Maternal Behavior From a Neuroendocrine Perspective
Summary and Keywords
For female mammals, caring for young until weaning or even longer is an extension of the reproductive burden that begins at insemination. Given the high price females potentially pay for failing to transmit genetic material to future generations, a multitude of interacting endocrine, neuroendocrine, and other neurochemical determinants are in place to ensure competent maternal caregiving by the time the offspring are born. Achieving this high maternal competency at parturition seems effortless but is quite a feat given that many nulliparous and parentally inexperienced female mammals are more prone to ignore, if not outright harm, conspecific neonates. There are important roles for ovarian steroids (e.g., estradiol and progesterone), adrenal steroids (e.g., glucocorticoids), and neuropeptide hormones (e.g., prolactin, oxytocin, arginine-vasopressin, and corticotropin-releasing factor) released during pregnancy, parturition, and postpartum in the onset and maintenance of caregiving behaviors in a broad range of commonly studied animals including rats, mice, rabbits, sheep, and primates. It is especially remarkable that the same collection of hormones influences caregiving similarly across these diverse animals, although to varying degrees. In addition to the well-known effects of hormones and neuropeptides on motherhood, more recent research indicates that experience-dependent epigenetic effects are also powerful modulators of the same neural substrates that can influence maternal responding.
For female mammals, caring for their young until weaning or even longer is an extension of the reproductive burden that begins at insemination. Given the high price that females potentially pay for failing to transmit genetic material to future generations, a multitude of interacting endocrine, neuroendocrine, and other neurochemical determinants are in place to ensure competent maternal caregiving by the time the offspring are born. Achieving this high maternal competency at parturition seems effortless but is quite a feat given that many nulliparous and parentally inexperienced female mammals are more prone to ignore, if not outright harm, conspecific neonates.
The endocrine and neuroendocrine factors driving positive maternal responding to offspring have been particularly well studied in laboratory rats and mice, rabbits, and sheep. There are also some compelling studies addressing this topic in non-human and human primates. The scientific literature on the hormonal control of motherhood has been reviewed many times in detail (e.g., Barrett & Fleming, 2011; Bosch & Neumann, 2012; Bridges, 2015; Lonstein et al., 2014; Saltzman & Maestripieri, 2011; Stolzenberg & Champagne, 2016), so the goal of this article is instead to highlight some of the seminal work that laid the foundations of this field and then selectively review research mostly from the 2000’s that has saliently advanced our understanding of the endocrine and neuroendocrine mechanisms underlying motherhood. Although this review focuses on maternal caregiving in a few mammalian models, taking care of offspring is certainly not exclusive to mothers or mammals. Indeed, 3% to 5% of mammalian fathers (most often including some species of primates, rodents, and canines) live in monogamous social structures that typically involve paternal behavioral investment in the young (Kleiman, 1977). Furthermore, nest attendance, protection, and offspring feeding is characteristic of both sexes of birds (Cockburn, 2006). Parental care in a variety of forms is also exhibited by one or both sexes of some fish (Mank et al., 2005), amphibians (Crump, 1996), reptiles (Gans, 1996), and even invertebrates such as insects (Trumbo, 2002). While the neuroendocrine control of parenting by fathers or non-mammals are fascinating topics, the readers are referred to other sources for coverage of these scientific literatures (Angelier et al., 2016; Bales & Saltzman, 2016; Fernandez-Duque et al., 2009; Mas & Kölliker, 2008; Storey & Ziegler, 2016; Trumbo, 2002).
Measures of Maternal Care
Laboratory rats and mice are the most-often studied animals for understanding the endocrinology and neuroendocrinology of maternal care. They display a similar constellation of caregiving behaviors that ensure the survival of their immobile and immature pups. The repertoire of caregiving activities commonly measured in rats and mice includes motorically active behaviors usually involving the mother’s mouth. For instance, dams use their mouths (along with their paws) to construct and maintain a nest where interactions with the litter will most often occur. They also use their incisors to gently carry offspring to the nest or reposition them within it, and they clean pups by licking their anogenital region and other parts of their bodies. While engaged in these oral caregiving or non-caregiving activities (e.g., self-grooming, eating), mothers hover over the young in the nest, which allows the pups to find and attach to mothers’ teats; if a sufficient number of pups attach and begin suckling, the highly active maternal caregiving behaviors just described give way to maternal bouts of quiescent nursing. All of these behaviors are readily shown within a laboratory setting, and their quantity and quality can be reliably measured (Kuroda & Tsuneoka, 2013; Lonstein & Fleming, 2002). Two general paradigms are used to do so: (1) separating the mother from her litter and conducting an observation after their reunion and (2) undisturbed observation. Mother-litter separations can range from minutes to hours, with longer separations increasing maternal motivation and ensuring high levels of rapidly displayed caregiving when the litter is returned. The separation/reunion paradigm is particularly useful because it elicits the entire suite of maternal behaviors (especially retrieval of scattered pups) within a relatively short test period. Because forced separation and reunion is unnatural, this paradigm best reflects maternal motivation and behavior under mildly challenging conditions. On the other hand, undisturbed observations of maternal caregiving involving periodic assessment of ongoing behaviors every few seconds or minutes over 5 to 30 minutes a few times each day are particularly informative for telling us what dams choose to do under relatively unstressed conditions and what the offspring more typically experience over their development within the lab. Importantly, the separation-reunion and undisturbed paradigms are most useful when used together, because retrieval of pups is not correlated with most other maternal caregiving behaviors even within the same test paradigm (i.e., retrieval is a poor proxy for all facets of mothering, see Slotnick, 1967), and in studies where the same dams are observed under both the separation-reunion and undisturbed paradigms, their behaviors toward the pups are not significantly correlated between tests (Champagne et al., 2007; Rocha, Soares, & De Mello, 2002; Rowell, 1960).
Under undisturbed conditions, nursing is the most frequently displayed maternal behavior by laboratory rats, mice, and many other mammals (Champagne et al., 2003; Grieb, Tierney, & Lonstein, 2017; Grota & Ader, 1974). Nursing in rats and mice is characterized by prolonged cessation of movement because dams cannot successfully nurse while engaging in activities that could dislodge pups from the teats. Their nursing behavior involves at least three distinct postures: (1) upright kyphosis that involves the dams standing over the litter with stiff, splayed limbs and a low- or high-arched back, (2) a more relaxed prone or “blanket” position over the litter in the absence of limb rigidity, and (3) passively lying on the side or back in a supine position with the pups attached to the exposed teats. During early lactation, kyphosis is the predominant nursing posture and is almost exclusively when milk letdown occurs (Lonstein, Simmons, & Stern, 1998; Stern & Levine, 1972). As such, kyphosis alone is sometimes used as a measure of the quality of maternal care (Bosch, 2011). Nursing in the prone and supine positions are more common during long nursing bouts, presumably because kyphosis is fatiguing. Supine nursing in particular becomes the predominant nursing position during late lactation when older litters can both no longer fit under their dams if she is standing and are motorically capable of attaching to teats and suckling with minimal maternal assistance (Stern & Johnson, 1989).
In addition to these caregiving behaviors directed toward the offspring, mothers also contribute to offspring survival in the important albeit indirect way of maternal aggression (Bosch, 2013; Lonstein & Gammie, 2002). While the term could imply aggressive behavior toward the offspring, it is rather the opposite, with mothers vigorously defending their young and territory against potentially threatening intruders. Maternal aggression has often been studied in the laboratory and can be affected by a number of testing conditions including the stage of lactation, sex and gonadal status of the intruder, the recent presence of the pups, and the duration of testing (Bosch 2013; Lonstein & Gammie, 2002).
The ethogram of behaviors and testing paradigms just described may be ideal for studying maternal caregiving in many small laboratory rodents, but not for all animals because caregiving is often species specific. For example, rabbit mothers interact with their pups only once a day to nurse them for a three-minute bout, do not retrieve pups if they stray from the nest, and their nest building involves unique hair pulling in addition to digging and carrying other nesting material (González-Mariscal et al., 2016; Hudson & Distel, 1982). Another example is that female sheep certainly do not carry their young, do not build nests, nor lick their lambs much after an initial post-parturitional cleaning. Ewes are instead observed for behaviors reflecting the selective bond they form with their lamb, including emission of vocalizations that either invite or dissuade lambs’ suckling attempts, firm kicks that reject unrelated lambs, and acceptance of their own lambs at the teat and subsequent nursing (Poindron & Le Neindre, 1980).
In studies involving caregiving in humans, maternal sensitivity is typically studied. Although maternal sensitivity is inconsistently defined (Shin et al., 2008), it often involves measures of behaviors that postpartum women typically engage in with their infants (dyadic mother-infant vocalizations, positive affect, gaze, touch) as well as behaviors that may indicate the quality of the mother-infant relationship (concordance between mother’s response and infant’s signal, the degree to which a regulatory context is provided for the infant, maternal consistency, and adaptation to infant’s signals). Thus, maternal sensitivity measures provide rich information about how the mother-infant dyad functions both at rest and during infant distress.
Neuroendocrine Basis of Motherhood—Ovarian and Adrenal Steroid Hormones
Steroid Hormone Effects in Laboratory Rats and Mice
An endocrine facilitation of motherhood can be assumed based on the fact that, while many juvenile female mammals show spontaneous caregiving of younger siblings or unrelated neonates (Bridges et al., 1974; Brunelli, Shindeldecker, & Hofer, 1985; Frodi et al., 1984; Maestripieri & Pelka, 2002), adult females without any previous maternal experience are instead more likely to ignore or harm young when introduced to them for the first time. However, it should be noted that while the neuroendocrine events of pregnancy and parturition are the most effective for inducing maternal behavior in rats and mice, they are not absolutely necessary. Even most maternally avoidant nulliparous rats will often overcome their hesitation and show surprisingly apt caregiving (except providing milk, of course) (Fleming & Rosenblatt, 1974; Lonstein, Wagner, & De Vries, 1999) through a non-hormonal process termed maternal sensitization. Maternal sensitization in laboratory rats involves five to seven days of continuously exposing nulliparous females to cohorts of young pups before the full effect is observed, and this process does not require the ovaries, pituitary, or adrenal glands (Rosenblatt, 1969). In addition, nulliparous female mice of some strains are spontaneously maternal, and reproduction has only a relatively small enhancing effect on their caregiving behaviors (Stolzenberg & Rissman, 2011).
Early studies in rats demonstrated that continuously transfusing blood between virgin and gravid rats for as little as the six hours surrounding parturition could elicit retrieval in the nulliparae about ten hours later (Terkel & Rosenblatt, 1972). Although the specific blood-borne factors driving the onset of caregiving were unclear, subsequent work revealed that pregnancy in rats (and other animals including mice, rabbits, and sheep) was characterized by chronically high circulating progesterone in the face of low to moderate levels of estradiol, followed by their reversal at parturition (i.e., progesterone falls while estradiol rises) (Bridges, 1984) (McCormack & Greenwald, 1974; Rosenblatt & Siegel, 1981a). In rats and mice, this pattern of ovarian hormone release is conducive for both maternal caregiving and the postpartum estrus occurring within hours after giving birth, which allows these short-lived animals to reproduce quickly (Connor & Davis, 1980a, 1980b; Dewsbury, 1990). Interestingly, the regulators of circulating estrogens and progesterone shift across pregnancy from the maternal ovaries to the placentae. By mid-to-late pregnancy, the rat placentae produce much of the androgens aromatized into the dams’ circulating estradiol and produce the luteotrophin necessary for her progesterone release; surgically removing placentae along with the fetuses decreases both circulating estrogen and progesterone titers in gonadally intact mothers (Bridges, Rosenblatt, & Feder, 1978; Gibori & Sridaran, 1981; Pepe & Rothchild, 1972; Sridaran, Basuray, & Gibori, 1981).
Evidence for the critical role of estrogens and progestins in the induction of maternal care comes from studies that administered exogenous estradiol (the primary circulating estrogen in pregnant rats and probably other rodents) (Biswas et al., 1991; De Lauzon et al., 1974) and progesterone to nulliparous ovariectomized rats and found high levels of caregiving behaviors toward test pups within 24 hours after treatment concluded. Note that this hormone regimen was capable of inducing maternal care even when the hormones were given over a curtailed period of just 14 days (Bridges, 1984). Administering both hormones is ideal, because while two weeks of estradiol exposure alone can facilitate the onset of pup retrieval in virgin rats, it is only effective at supraphysiological doses (Bridges, 1984), suggesting that progesterone synergizes with estradiol to maximize estradiol’s effects. While progesterone at first synergizes with estradiol to promote motherhood in nulliparous rats, progesterone must later be withdrawn or else the onset of caretaking behavior is instead inhibited (Bridges, 1984; Numan, 1978; Sheehan & Numan, 2002). Progesterone withdrawal at parturition is also necessary for the onset of maternal behavior in parous rats, as experimentally extending high circulating progesterone levels at parturition inhibits the onset of caregiving (Numan, 1978; Siegel & Rosenblatt, 1978). However, just administering and then withdrawing progesterone in the absence of estrogen priming does not instill maternal behavior in rats (Doerr, Siegel, & Rosenblatt, 1981). These facilitatory and then inhibitory effects of progesterone on the onset of maternal behavior is reminiscent of progesterone’s biphasic effects on female copulatory behavior: such that it first synergizes with estradiol to promote lordosis, but its continued presence or later reappearance inhibits females’ estrus behavior (Blaustein & Wade, 1977; Marrone, Rodriguez-Sierra, & Feder, 1977).
Rat and mouse models manipulating the estrogen receptor gene (Esr1) further establish the importance of estrogen signaling for maternal caregiving. Because full-body null mutation of all estrogen receptors (ERs) results in infertility (Dupont et al., 2000; Korach, 1994), its effects on maternal responding have only been tested in nulliparous mice. These ER “knockout” (ERKO) females are less responsive to pups compared to controls (Ogawa et al., 1996), and a similar effect is found in female mice with knockout of just the ER alpha isoform (ERα). This was true whether or not the females were gonadally intact, suggesting that another source of estradiol is relevant for their pup-directed behavior (Ogawa et al., 1998). Interestingly, nulliparous female mice with whole-body knockout of the aromatase enzyme that cannot synthesize testosterone from its primary precursor estradiol show maternal responsiveness similar to their wild-type sisters (Stolzenberg & Rissman, 2011). Systemic injection of an aromatase inhibitor to adult ovariectomized mice of the same C57/BL6 strain, however, does depress retrieval of pups and nest building (Murakami, 2016). These results could suggest that the lifelong loss of estradiol synthesis from a knockout permitted some compensation that is not possible after acute loss of estradiol synthesis with the aromatase inhibitor, that other forms of functional ERs remain in the ERKO mice or that ERs promote caregiving through mechanisms other than their ability to bind estradiol, perhaps involving ligand-independent stimulation of the receptors (Hart & Davie, 2002). While most studies of estrogen’s positive effects on maternal caregiving imply that the hormone does so through slow-acting cytoplasmic ERs that precipitate changes in protein synthesis, this may not always be true. A single injection of a water-soluble form of 17β-estradiol, which presumably acts only at the cell membrane, given when pups are first presented further facilitates maternal behavior in female rats that are hormonally primed through a partial pregnancy followed by its termination (Stolzenberg et al., 2009).
ERs are expressed widely across the brain (Merchenthaler et al., 2004; Österlund et al., 2000; Shughrue, Lane, & Merchenthaler, 1997; Simerly et al., 1990), and their expression changes in numerous hypothalamic and limbic sites across female reproduction (Greco, Lubbers, & Blaustein, 2003; Koch & Ehret, 1989; Wagner & Morrell, 1995). Thus, although there are probably many brain areas where estradiol acts to promote maternal behaviors, this has been demonstrated only for the medial preoptic area (mPOA). Implanting cannulae containing estradiol into the mPOA elicits a rapid onset of pup retrieval in virgin or pregnancy-terminated female rats (Fahrbach & Pfaff, 1986; Felton et al., 1999; Numan, Rosenblatt, & Komisaruk, 1977) and stimulates nest building in ovariectomized rabbits (González-Mariscal et al., 2005). Conversely, implanting a cannula filled with the mixed ER antagonist, tamoxifen, into the mPOA two days before parturition slightly delays the onset of maternal behavior in rats (Ahdieh, Mayer, & Rosenblatt, 1987) and short hairpin interference of ERα mRNA in the mPOA beginning before mating greatly interferes with later postpartum caregiving during brief retrieval tests in mice (Ribeiro et al., 2012). ER-sensitive cells in the mPOA project to many brain areas involved in mothering (Fang et al., 2018; Morrell et al., 1984), including dopaminergic and non-dopaminergic cells of the ventral tegmental area (VTA) (Morrell et al., 1984; Tobiansky et al., 2016). As with other goal-direct behaviors, the VTA is involved in the dopamine release essential for the motivation to act maternally (Numan & Smith, 1984; Numan & Stolzenberg, 2009; Numan et al., 2009). Studies in nulliparous and lactating mice revealed that optogenetic inhibition of mPOA ERα-expressing cells that project to the VTA severely impairs retrieval, while stimulating those cells caused females to stop nursing, depart the nest, and explore objects in the cage (pup or inanimate) or the test cage itself (Fang et al., 2018).
Progestin receptor (PR) expression in numerous hypothalamic sites, including the mPOA, increases sharply at the end of pregnancy and at parturition but declines postpartum in rats and mice (Francis et al., 2002; Grieb et al., 2017; Numan et al., 1999). Mice with life-long singular or combined null mutations of the A and B isoforms of the PR have been generated, but not yet tested for maternal caregiving. Loss of only PR-B does not prevent reproduction (Mulac-Jericevic et al., 2003), so the postpartum behaviors of such females could be studied. Some insight into the role of PR in maternal behavior is provided by the greatly reduced infanticide and increased caregiving by male mice without PR-A or PR-B (i.e., PRKO mice), supporting previous research that PR signaling can inhibit, as well as promote, caregiving behaviors. Perhaps surprisingly, it is still unknown where in the brain progesterone facilitates or inhibits caregiving in laboratory rodents. The only study in rats examining this (Numan, 1978) implanted progesterone into the mPOA (or the ventromedial hypothalamus, midbrain tegmentum, or raphe nuclei), but it did not delay maternal responding in pregnancy-terminated rats. Application or withdrawal of progesterone in the mPOA also does not affect nest building in ovariectomized rabbits primed with estradiol (González-Mariscal et al., 2005). Either the most relevant sites of progesterone action have not been identified, or its effects are spread across multiple brain sites that would need to be simultaneously targeted.
After parturition, circulating levels of both estradiol and progesterone are very low for at least the first three to five days postpartum (Hansen, Sodersten, & Eneroth, 1983; Taya & Greenwald, 1982). Because of this, it has long been believed that the maintenance of maternal behavior after its periparturitional onset is independent of hormones and instead controlled by sensory cues that mothers receive from their offspring (Rosenblatt & Siegel, 1981b). This is certainly true at a gross level because ovariectomy does not cause postpartum female rats or mice to completely desist caregiving (de Sousa et al., 2010; Grieb et al., 2017), and long separations from offspring degrade dams’ later responsiveness to them (Bridges & Scanlan, 2005; Fleming & Sarker, 1990). Even so, circulating progesterone levels rise more than five-fold between the day after parturition and mid-lactation in rats, then gradually fall again (Hansen et al., 1983; Smith & Neill, 1977). This change in postpartum progesterone is behaviorally relevant because postpartum rats without ovaries display less pup licking during early lactation but show more pup licking, hovering over the litter in the nest, and nursing during mid-to-late lactation (de Sousa et al., 2010; Grieb et al., 2017). Furthermore, pup licking by mid-to-late postpartum rats is negatively correlated with PR-A mRNA expression in the mPOA, while kyphotic nursing is negatively correlated with their mPOA PR-B mRNA expression (Grieb et al., 2017), suggesting that even long after parturition PR signaling in the mPOA may still influence motherhood.
Circulating adrenal corticosterone (the major adrenal glucocorticoid in rats and mice) increases during late pregnancy and reaches its highest levels at parturition. It then decreases dramatically postpartum to levels similar to those of early pregnancy, though the typical diurnal rhythms in corticosterone release are blunted (Atkinson & Waddell, 1995). Glucocorticoids are not absolutely necessary for the performance of maternal behaviors because adrenalectomized dams initiate and sustain caregiving activities (Thoman & Levine, 1970). Adrenal hormones probably support the completeness of mothering behavior, though, as female rats adrenalectomized during late pregnancy show deficits in their early postpartum pup retrieval (Hennessy et al., 1977) and the presence of adrenal glands facilitates caregiving after pregnancy termination (Siegel & Rosenblatt, 1978) or after parturition (Rees et al., 2004). However, adrenal hormones have also been seen to be negatively associated with the onset of maternal behavior in sensitized virgin rats (Leon, Numan, & Chan, 1975; Rees et al., 2006). Such results could indicate that corticosterone has opposite effects on maternal responding in naturally reproducing female rats and nulliparous sensitized rats.
Because the deficits in maternal caregiving by adrenalectomized, reproducing rats can be reversed when corticosterone is replaced through drinking water, the maternal deficits appear to be glucocorticoid specific (Rees et al., 2004). Consistent with these findings, daily administration of corticosterone via intraperitoneal injection reduces nursing in rats (Brummelte, Pawluski, & Galea, 2006) and acute administration of the synthetic glucocorticoid, dexamethasone, impairs both pup retrieval and nursing. Dexamethasone injections also decrease maternal levels of circulating prolactin (PRL) and oxytocin (OT) following suckling by pups, two peptides that play an important positive role in mothering (Vilela & Guasti-Paiva, 2011). Together this work supports the idea that corticosterone is not necessary or sufficient for the onset and maintenance of maternal caregiving in rats but modulates the behavior.
Notably, early to mid-lactation is a time of endocrine and behavioral hyporesponsiveness to stress in laboratory rats and some other mammals. These females show blunted central nervous system, and hypothalamic-pituitary-adrenal (HPA) axis, responsiveness to stressors (Brunton & Russell, 2011; Slattery & Neumann, 2008). This postpartum hyporesponsiveness to stress depends on the environment, though, because in the presence of pups it has been found that postpartum rats still show a strong HPA response to a very salient stressor such as predator odor (Deschamps, Woodside, & Walker, 2003). Relevant to the work showing that exogenous corticosterone decreased maternal behaviors, exogenous administration of corticosterone also decreases neurogenesis in the hippocampus (Workman et al., 2016). Thus, corticosterone is likely facilitating neuronal changes in the postpartum brain that may alter maternal stress response to contextual cues, with consequences for females’ caregiving behaviors.
Steroid Hormone Effects in Rabbits
Similar to other small mammals that give birth to multiple young, maternal caregiving in rabbits begins by creating a nest in which the doe will interact with her pups. This nest building involves the mid-pregnant mother first digging into the ground to create a burrow. A few days later she carries straw to the burrow and shapes it into a nest, and finally on the day before parturition and for a few days postpartum plucks out her ventral and lower-limb hair—which is loosened by the effects of high circulating testosterone on the follicles—to softly line the nest (González-Mariscal et al., 1994). Does spend five to seven minutes caring for their litters after giving birth to them, but thereafter only spend an amazing two to three minutes each day interacting with the offspring during a single, brief nursing bout in the upright kyphotic posture (González‐Mariscal et al., 2013). This maternal investment is clearly different from early-postpartum laboratory rats, which are in the nest with pups for >80% of their time (Grota & Ader, 1969). Given the extremely short window in which the rabbit pups can suckle, starting an hour before the dams’ expected arrival at the same time each day, the pups spontaneously wiggle to the surface of their nesting material and aggregate together. These pup behaviors maximize their access to teats once their mother arrives and minimizes the doe’s time in the nest that otherwise would be spent finding and moving pups around the nest (Hudson & Distel, 1982). Carrying and licking the pups are rarely observed during mother-litter interactions in rabbits, so are not often recorded by researchers.
Nulliparous rabbits are not at all maternal and resistant to pup-induced maternal sensitization (Gonzalez-Mariscal et al., 2004). Thus, the onset of maternal caregiving behaviors in this species absolutely depends on exposure to circulating steroids and other hormones across pregnancy and parturition. Unlike rats, the rabbit placenta is probably not a major source of steroids during pregnancy, and the ovaries themselves are most important throughout reproduction (Gadsby, Keyes, & Bill, 1983). Estradiol is the primary estrogen in the peripheral plasma of pregnant rabbits, but its levels are not much higher than circulating estrone. There are no fold-changes in the levels of estradiol (nor estrone) across most of pregnancy in rabbits, although estradiol rises somewhat through the middle of pregnancy and more so at the very end of pregnancy (by ~50%–75% compared to the first third of pregnancy; (Challis, Davies, & Ryan, 1973; González-Mariscal et al., 1994). By contrast, circulating progesterone increases by about 400% between insemination and the middle of pregnancy and then gradually falls. Together, these shifts in ovarian hormones reduce the circulating progesterone to estradiol ratio quite dramatically by the time of parturition, which is generally similar to that seen in reproducing female rats and mice (Challis et al., 1973; González-Mariscal et al., 1994).
Correlations between the levels of these ovarian hormones across pregnancy and does’ behavior include: a slow increase and fall in digging associated with the slow rise and later mid-pregnancy drop in circulating progesterone, straw carrying that begins late in pregnancy as progesterone continues to fall and estradiol makes its small rise, and an abrupt onset of hair pulling coinciding with the peak in estradiol and near nadir levels of progesterone just before parturition (González-Mariscal et al., 1994). In ovariectomized rabbits, three weeks of exogenous estradiol given along with progesterone that is withdrawn a few days before testing induces all three components of nest building (Zarrow et al., 1963). More detailed analyses show that estradiol-treated females start digging within four days of progesterone treatment and that the behavior drops when progesterone is withdrawn; straw carrying begins about four days later and hair pulling in some does begins around the same time (Gonzalez-Mariscal et al., 1996).
As mentioned earlier, the mPOA is a site of estradiol’s actions for maternal behaviors in does. Implanting estradiol into the mPOA and the surrounding region of ovariectomized rabbits given peripheral progesterone leads to digging behavior in most of them, and straw-carrying is seen when the progesterone is withdrawn. Progesterone-stimulated digging also emerges when the estradiol implants are in the nucleus accumbens, but not if they are in the hippocampus (González-Mariscal et al., 2005). However, neither progesterone implanted into the mPOA nor its withdrawal stimulates any nesting behaviors when females are given peripheral estradiol (González-Mariscal et al., 2005), further indicating that the mPOA is alone sufficient to generate estradiol’s effects on nesting behavior in rabbits. While these results could suggest that the mPOA has little role in progesterone’s effects on nestbuilding, a 2018 study showed that lesioning the mPOA and surrounding region of gonadally intact rabbits prevents progesterone-stimulated digging as well as hair pulling after progesterone’s withdrawal. In ovariectomized rabbits given peripheral estradiol, mPOA lesions had no effect on progesterone-induced digging, but it did reduce their straw carrying and hair plucking after progesterone’s withdrawal (Basurto et al., 2018).
Steroid Hormone Effects in Sheep
Thus far, this article has described how the hormonal events of pregnancy and parturition promote the onset of mothering in species that give birth to litters, and therefore in females that do not form selective attachments with their young. In other words, the hormonal context of reproduction in these species functions to induce caregiving responses toward any infant. Once this maternal state has been induced, mothers provide indiscriminate care to young. By contrast, herding animals such as sheep and other ungulates are seasonal breeders, and many females within the herd give birth to precocial or mobile young around the same time. To avoid maternal investment in unrelated young, in these herding species, the onset of maternal behavior is soon followed by a highly selective display of caregiving behaviors toward their own offspring. For instance, ewes are particularly well studied for forming a selective attachment to their lamb at birth and subsequently rejecting or even aggressing against unrelated lambs that attempt to suckle (Poindron & Le Neindre, 1980).
Despite this striking difference in their maternal behaviors, the hormonal mechanisms initiating maternal care in sheep are quite similar to those described in laboratory rats, mice, and rabbits. The circulating pattern of steroid hormones driven by the placenta in late pregnancy is conserved in sheep, such that high estradiol coupled with progesterone withdrawal coincides with the birth of young (Chamley et al., 1973; Poindron & Le Neindre, 1980). Like most rats and rabbits, sheep reject all young before giving birth and the hormonal context of birth promotes attraction to and acceptance of an infant. However, the hormonal profile of parturition in ewes must be coupled with vaginocervical stimulation (naturally induced by delivery of the fetus) in order to promote a rapid onset of mothering. Vaginocervical stimulation during labor induces central release of OT, which in the context of steroid priming is necessary for the onset of their maternal care (Da Costa et al., 1996; Kendrick, Keverne, & Baldwin, 1987; Kendrick et al., 1992b). Like rabbits, sheep typically do not show maternal sensitization, and hormone priming even when coupled with mechanical vaginocervical stimulation is unlikely to induce a rapid onset of maternal care in non-pregnant ewes unless they are maternally experienced (Kendrick, Levy, & Keverne, 1991; Le Neindre, Poindron, & Delouis, 1979; Poindron & Le Neindre, 1980). The primary brain site where OT promotes the onset of maternal care in ewes is the paraventricular nucleus of the hypothalamus (PVN) rather than the mPOA (Da Costa et al., 1996; Kendrick et al., 1992b), although both the onset and maintenance of maternal behavior in ewes (as in rats/mice/rabbits) requires a functioning mPOA (Perrin, Meurisse, & Levy, 2007).
Recently parturient ewes will care for any lamb, but within three hours of delivery ewes learn to distinguish their own lambs from alien young, at which point an attachment is formed and caregiving becomes selective (Poindron & Le Neindre, 1980). Thus, the onset of maternal care precedes the onset of maternal selectivity, but both processes occur within hours of parturition under the same physiological circumstances. This short time window suggests that the hormonal events that promote infant access to maternal neural circuits may also be involved in the subsequent gating of alien infant cues to these circuits. In support of this idea, administration of estradiol, progesterone, and mechanical vaginocervical stimulation promotes both the onset of maternal behavior as well as selective lamb attachment in maternally experienced, non-pregnant ewes (Kendrick et al., 1991).
Whereas the hormonal events of birth act upon hypothalamic nuclei to initiate caregiving behavior (Kendrick et al., 1992b; Perrin et al., 2007), it is hormonal action within the olfactory system that gates which sensory cues gain access to the maternal circuit. While plasticity within multiple sensory systems contributes to infant discrimination, it is recognition of cues transmitted by the main olfactory system that is critical for mother-infant bond formation in sheep (Lévy et al., 1995). In the main olfactory system, odors are first detected by sensory neurons in the main olfactory epithelium of the nasal cavity. These sensory neurons synapse on mitral cells in main olfactory bulb (MOB), which then project centrally to a number of targets including the anterior olfactory nucleus, piriform cortex, entorhinal cortex, and cortical amydala (Dulac & Wagner, 2006). Plasticity within the main olfactory system mediates offspring recognition by permitting sensory cues from one’s own infant to activate maternal neural circuits while preventing cues from alien young to do so. Anosmic postpartum ewes that lack the ability to detect odor cues because of experimental damage to the olfactory epithelium can no longer discriminate between own and alien young, and instead care for all offspring (Lévy et al., 1995). Thus, unlike maternal selectivity, maternal caregiving behavior does not rely on olfaction. Therefore, unique neurobiological adaptations that coincide with selective attachment can be teased apart from those adaptations that coincide with maternal care. For example, a comparison of immediate-early gene activity in fully maternal, selectively attached ewes (normal) with fully maternal indiscriminate ewes (anosmic), indicated that central targets of the main olfactory system (piriform cortex, medial and orbital frontal cortex, entorhinal cortex, and cortical amygdala) were the only regions that showed unique activation in selectively attached ewes (Keller et al., 2004a). This work supports the idea that maternal behavior and maternal attachment are separate processes. Interestingly, electrophysiological recordings from mitral cells in the MOB of ewes during the last two months of pregnancy showed that not a single mitral cell responded to infant odors, whereas following parturition 60% of these same cells in these same ewes responded to infant odors (Kendrick et al., 1992a). Importantly, the increase in mitral cell response and the subsequent transmission of lamb olfactory cues was critical for selective attachment because interference with the MOB or some of its targets (the cortical and medial amygdala, the entrorhinal cortex) prevented maternal selectivity, but not maternal care (Keller et al., 2004b; Sanchez-Andrade & Kendrick, 2009).
Interestingly, mitral cells that were unresponsive to infant odors during pregnancy became preferentially responsive to infant odors over food odors following birth (Kendrick et al., 1992a). Further, a subset of these mitral cells responded exclusively to infant cues from the ewe’s own offspring. This work suggests that the physiological context of birth might mediate a critical period of plasticity within the MOB that allows ewes to learn the odor of their lamb. In support of this idea, the altered electrophysiological responses of mitral cells in parturient ewes were accompanied by changes in norepinephrine (NE). Further, NE is induced during the vaginocervical stimulation of birth and is critical for olfactory recognition and selective attachment (Kendrick et al., 1992a; Levy et al., 1990; Levy et al., 1997; Lévy et al., 1995).
The data just described suggest a mechanism through which vaginocervical stimulation at parturition mediates the plasticity in the main olfactory system that drives selective attachment. However, vaginocervical stimulation-induced release of NE requires prior estradiol priming. Thus, the surge of estradiol at birth also likely contributes to olfactory learning, although these mechanisms are largely unknown. Most of what is known about the role of estradiol in social recognition comes from work done in mice. Deleting ERα impairs recognition of conspecifics (Sanchez-Andrade & Kendrick, 2011), and ERα is expressed in sites that regulate olfactory recognition including the MOB (Meurisse et al., 2005). One possibility is that ERα activation in the MOB plays influence sex citatory/inhibitory activity through the transcriptional regulation of both glutamate and GABA receptor subunits (Guerra-Araiza et al., 2008).
Steroid Hormone Effects in Humans and Some Other Primates
The profiles of circulating estrogens and progestins in pregnant and parturient humans and other Homininae are similar to each other but are often thought to differ from laboratory rats, mice, rabbits, and sheep. Women with healthy pregnancies show rising levels of estrogens and progesterone during early pregnancy that are within menstrual cycle ranges until about week seven or eight, after which the levels rapidly rise and remain high throughout the rest of pregnancy (Darne, McGarrigle, & Lachelin, 1987; Mathur, Langrebe, & Williamson, 1980; Tulchinsky & Hobel, 1973). While a number of studies have found that progesterone levels are the same before, during, and soon after delivery—thus disputing the idea that withdrawal of a “progesterone block” triggers the momentous event (Lofgren et al., 1997; Luisi et al., 2000; Mathur et al., 1980; Tulchinsky et al., 1972; Willcox et al., 1985)—a major study involving 500 women, and sophisticated statistical modeling of their hormone trajectories across pregnancy and parturition found that plasma progesterone does in fact decrease compared to predicted values between the month before and during delivery for most women and that levels of the relatively “weak” estrogen, estriol, surged producing an elevated peripartum ratio of estrogens to progestins that is reminiscent of what is found in the other peripartum animals already discussed (Smith et al., 2009) also see (Keresztes et al., 1988; Mathur et al., 1980; McGarrigle & Lachelin, 1984) for peripartum changes in estriol or E:P ratios (Keresztes et al., 1988; Mathur et al., 1980; McGarrigle & Lachelin, 1984; Smith et al., 2009). Estriol’s precursor in pregnant women and other hominids is dehydroepiandrosterone sulfate (DHEAS) synthesized by the developing fetal adrenal gland, which is then converted to estriol within the placenta (Goodwin, 1999); most maternally circulating progesterone comes from the placenta. The large study just mentioned by Smith et al. (2009) as well as work by others (McGarrigle & Lachelin, 1984; Willcox et al., 1985) report estriol as the primary circulating estrogen during much or at least the end of pregnancy in humans, but smaller studies have reported that levels of estradiol are similar or even higher than estriol (Keresztes et al., 1988; Mathur et al., 1980; Tulchinsky et al., 1972; Tulchinsky et al., 1975). The specific times that the samples are taken, the particular estrogens and progestins assayed, whether free or bound hormones are measured, subject parity and the source of the maternal samples (plasma, saliva, urine) probably contribute to these and other apparent discrepancies in this scientific literature. Nonetheless, suckling by infants after birth strongly suppresses maternal release of gonadotropin-releasing hormone, and regular breastfeeding can suppress circulating estrogens and progestins (and therefore ovulation) for a few years postpartum (Diaz et al., 1995; McNeilly, 2001).
Similar to women, pregnant gorillas experience rising plasma estrogens and progestins that peak a month or two before parturition, which then notably decline in most females the day before or the day of parturition (Bellem, Monfort, & Goodrowe, 1995; Czekala et al., 1983; Hopper, Tullner, & Gray, 1968; Seaton, 1978; Smith et al., 1999). In terms of absolute levels, estriol is also a primary—if not the primary—circulating estrogen during much of pregnancy in gorillas (Albrecht & Pepe, 1990; Bellem et al., 1995; Hopper et al., 1968). Importantly, this is not true of all non-human primates because pregnant rhesus monkeys or baboons do not have detectable estriol (Albrecht, Haskins, & Pepe, 1980; Hopper et al. 1968). Levels of all estrogens and progesterone are very low within a few days after parturition in gorillas (Bahr et al., 2001; Bellem et al., 1995; Hopper et al., 1968) and remain low at least through the first few weeks of lactation (Bahr et al., 2001). Pregnant and parturient chimpanzees show similar hormone patterns as humans and gorillas (Shimizu et al., 2003; Smith et al., 1999; Steinetz et al., 1992), although one study reported that estriol does not dominate as the primary estrogen during the first half of pregnancy and only slightly exceeds the high levels of estradiol during the second half (Reyes et al., 1975).
How the ratios between circulating estrogens and progestins during pregnancy and parturition are related to later maternal caregiving in primates is equivocal. Suggestive of a hormonal contribution, positive attitudes about infants and attraction to them or their disassociated sensory cues are generally low in parentally inexperienced adult females, but increase during mid-to-late pregnancy in both humans and some non-human primates (e.g., (Fleming, Ruble, Krieger, & Wong, 1997b; Hrdy, 1977; Maestripieri & Wallen, 1995; Maestripieri & Zehr, 1998; Maestripieri & Pelka, 2002; Pryce, Dobeli, & Martin, 1993). Such increases in interest can also be modified by experiential factors including parity (Saltzman & Abbott, 2005) and social rank (Maestripieri & Wallen, 1995) in pregnant monkeys. To determine the relationships between hormones and maternal interest, a handful of studies have measured ovarian steroids or their metabolites across female reproduction and correlated them with displayed maternal behaviors. The rate of increased interest in other females’ infants by late-pregnant pigtail macaques is positively correlated with their circulating estradiol, as well as the estradiol:progesterone ratio, and this heightened interest could be reproduced in non-pregnant females by six weeks of exogenous estradiol (Maestripieri & Zehr, 1998). A generally positive relationship between pregnancy estrogens and either concurrent or postpartum maternal activities have also been found for Japanese macaques (Bardi et al., 2001; Bardi et al., 2003) and tamarins (Pryce et al., 1988), although high estradiol at the end of pregnancy is associated with lower infant survival in black tufted-ear marmosets (Fite & French, 2000). Late-pregnancy progesterone or its metabolites are positively associated with carrying and nursing by first week postpartum titi monkeys (Jarcho et al., 2012), and postpartum interaction with others’ infants in baboons (Ramirez et al., 2004). Significant relationships between prepartum estradiol or progesterone and infant-directed behavior have not been found for baboons (Bardi et al., 2004), rhesus macaques (Bardi et al., 2003), or gorillas (Bahr, Martin, & Pryce, 2001). Studies by Bardi et al. (2004) and others make the point that in socially and phenotypically heterogeneous primates, only a relatively small amount of the variance in mothering is likely to be explained by these circulating steroids, and that considering the more complete endocrine milieu during pregnancy and postpartum would be fruitful. Indeed, a pattern of high prepartum-to-low postpartum progesterone is associated with infant contact-seeking by female baboons, but only if maternal stress and cortisol are also taken into account (Bardi et al., 2004).
In women, estrogen and progesterone levels during pregnancy are unrelated to contemporaneous attitudes about the fetus and future infant (Fleming et al., 1997b); hormone levels during the first few days postpartum are similarly unrelated to contemporaneous maternal affectionate or caregiving behaviors (Fleming et al., 1987). However, pregnancy hormones do predict aspects of women’s later postpartum mothering. Unlike some of the studies on non-human primates already discussed showing positive relationships between high or changing estradiol and maternity, it is the women with the lowest estradiol:progesterone ratio mid-pregnancy, the least change in that ratio over time, and the lowest circulating estrogens that have the highest feelings of attachment with their infants during the first few days postpartum (Fleming et al., 1997b). Such effects are long lasting because the women with a lower estradiol:progesterone ratio and slower rise in estradiol across the last half of pregnancy—and a slower rise in progesterone through the last three weeks of pregnancy—were the most sensitive mothers even a year postpartum, but only if they had a daughter (Glynn et al., 2016). While these studies demonstrate that rate of change in estrogens and progestins during pregnancy influences maternal attitudes and sensitivity within days or a year of parturition, these hormones may act earlier in life to predispose some women toward high maternal attitudes even before conception. In a study of nulliparous young adult women, those with the most interest in having a large number of children had more feminine faces, which is associated with prenatal as well as adult hormone levels (Burriss, Little, & Nelson, 2007; Smith et al., 2006) and higher urinary estrogen metabolite levels (Law Smith et al., 2012).
As in laboratory rodents, adrenal steroid hormones increase across pregnancy in women and non-human primates. In particular, adrenocorticotropin-releasing hormone (ACTH) from the anterior pituitary, and cortisol from the adrenal glands, increase drastically from first to third trimesters and fall within the first few days postpartum (Campbell et al., 1987; Carr et al., 1981; Conde & Figueiredo, 2014; Jung et al., 2011). Corticotropin-releasing factor (CRF; also termed corticotropin-releasing hormone, CRH) levels also rise significantly across pregnancy and return to pre-pregnancy baseline within hours after labor (Campbell et al., 1987). Glucocorticoids and their metabolites also show this pattern in non-human primates such as cotton-top tamarins (Ziegler, Scheffler, & Snowdon, 1995), white-faced capuchins (Carnegie, Fedigan, & Zeigler, 2011), and baboons (Beehner et al., 2006; French et al., 2004; Oakey, 1975), among other primates (Edwards & Boonstra, 2017). This hypercortisolism has been attributed to the diminished ability of cortisol to convert to metabolites during pregnancy (Cohen et al., 1958), as well as a decrease in plasma levels of CRF-binding protein (Linton et al., 1993). The developing placenta, which secretes its own CRF along with other hormones (see section on prolactin), also contributes to a positive feedback loop that results in elevated maternal ACTH and cortisol across pregnancy (Glynn & Sandman, 2012; Glynn, Davis, & Sandman, 2013), further leading to maternal hypercortisolism.
Cortisol during pregnancy and postpartum influences primate maternal caregiving. Exogenous CRF or cortisol given during pregnancy reduces later maternal carrying by female marmosets (Saltzman & Abbott, 2009; Saltzman et al., 2011) and postpartum cortisol levels are positively associated with maternal caregiving in chimpanzees (Stanton et al., 2015). In women, steeper declines in diurnal salivary cortisol levels (Kivlighan et al., 2008), higher plasma cortisol (Gillespie et al., 2018), and higher 24-hour urinary cortisol levels (Conde & Figueiredo, 2014) are shown by primiparous, but not multiparous, mothers and are associated with maternal anxiety and distress (Gillespie et al., 2018; Kivlighan et al., 2008). In addition, there are ethnic differences in cortisol, ACTH, and CRF secretion during pregnancy (Glynn et al., 2007). In particular, pregnant African American women have lower circulating cortisol despite higher ACTH levels, as well as a dampened CRF and cortisol trajectory, compared to women of other ethnicities. Following labor, it is suggested that while collectively CRF, ACTH, and cortisol levels drastically fall, it can take months or even longer for HPA axis function to return to its pre-pregnancy state (Magiakou et al., 1996; Owens et al., 1987).
During the postpartum period in women, it is unclear whether high or low levels of total cortisol, or differences in daily decline patterns (blunted or steep), can promote maternal behavior. Higher salivary cortisol postpartum is associated with better recognition of and attraction to the odor of one’s own infant (Fleming, Steiner, & Corter, 1997a), particularly for primiparous mothers, as well as with maternal sensitivity, affectionate behaviors, and caregiving (Fleming, Steiner, & Anderson, 1987; Fleming et al., 1997a; Stallings et al., 2001). Women’s baseline and hormonal responses to infants are influenced by maternal environment factors, though, such as income (Tu, Lupein, & Walker, 2006), social support (Giesbrecht et al., 2013), and in particular the early life experiences of the mother (Barrett & Fleming, 2011; Gonzalez et al., 2012; Juul et al., 2016; Krpan et al., 2005). For example, postpartum women who reported adverse early life experiences tended to have higher morning cortisol levels and greater variation in their levels compared to women who did not report adverse early life experiences (Gonzalez et al., 2012). Such mothers exhibit relatively higher neutral affect and lower average cortisol during a mother-infant interaction task (Juul et al., 2016). A large study of low-income postpartum women across the United States found that an elevated index of poverty-related cumulative risk was positively associated with a positive maternal salivary cortisol slope during a parent-child interaction, though, and this effect remained above and beyond all tested demographic and perinatal characteristics. It was also found that maternal salivary cortisol slope was negatively associated with maternal sensitivity across the first two years postpartum (Finegood et al., 2016).
Maternal mood, which is associated with the quantity and quality of mother-child interactions, correlates with the patterns of maternal cortisol decline in some (Groer & Morgan, 2007; Handley et al., 1980; Taylor et al., 2009), but not all studies (Magiakou et al., 1996). However, the latter study did find a blunted cortisol response to CRF-stimulated ACTH in women with postpartum blues (Magiakou et al., 1996), suggesting alterations in HPA axis function but not total output during this time. More directly, a small study suggested elevated serum cortisol levels in women with postpartum depression relative to controls (Parry et al., 2003), although other studies have reported lower morning salivary cortisol levels in depressed mothers relative to non-depressed mothers (Groer & Morgan, 2007; Taylor et al., 2009). A study from last year found that higher levels of serum postpartum cortisol were associated with elevated postnatal depressive symptoms, but only for primiparous mothers (Gillespie et al., 2018). These apparent inconsistencies in the literature may be due to the timing and frequency of sampling, or the varying measures used to capture short-term HPA axis activity (i.e., saliva, plasma, urine).
Cortisol obtained from hair is a newer method to measure long-term HPA axis activity given that three centimeters of hair can estimate cortisol production of up to the three previous months (Kirschbaum et al., 2009). Thus, cortisol can be measured from hair collected at each trimester, and does follow the typical cortisol pattern found in plasma throughout the perinatal period (Kirschbaum et al., 2009; D’Anna-Hernandez et al., 2011). Higher concentrations of hair cortisol are associated with higher distress and depressive symptoms in mothers (Kalra et al., 2007; Caparros-Gonzalez et al., 2017), but this depends on the timing of symptom collection relative to length of hair evaluated (seven days versus one month). In addition, elevated maternal depressive symptoms were associated with higher hair cortisol in women who reported high levels of childhood adversity (Bowers et al., 2018), particularly among black women (Schreier et al., 2016). Work has yet to directly address the relationship between maternal hair cortisol concentrations and parenting, but together, the discussed work suggests dysregulation of the HPA axis is involved in postpartum affective disorders, although this also likely depends on the maternal environment.
Endocrine Basis of Motherhood—Peptide Hormones
Anterior pituitary extracts have long been known to elicit milk secretion from estrogen-primed mammary glands (Nelson & Pfiffner, 1930) and possibly promote maternal caregiving behaviors in nulliparous female rats (Wiesner & Sheard, 1933). Soon after the peptide was isolated from other anterior pituitary secretions (Riddle, Bates, & Dykshorn, 1933; Stricker, 1928), a role specifically for PRL in stimulating caregiving behaviors was explored in a variety of animals. While some found that it could enhance mothering when alone or in combination with other hormones in nulliparous rats and other animals (Riddle, Lahr, & Bates, 1935; Riddle, Lahr, & Bates, 1942; Zarrow et al., 1961; Lehrman, 1955), not all early studies on this topic found such effects (Baum, 1978; Beach & Wilson, 1963; Lott & Fuchs, 1962; Moltz et al., 1970).
Subsequent work more clearly defined the role of PRL in facilitating the onset of mothering in postpartum rats and other small laboratory animals, but it is probably not absolutely necessary. Peripheral administration of PRL reduces the latency for nulliparous, ovariectomized rats to become maternally sensitized following both estradiol and progesterone treatment (Bridges et al., 1985; Bridges et al., 1990; Bridges et al., 1997). Impairing pituitary PRL release in hormone-treated, sensitized virgins with a dopamine receptor agonist delays their onset of maternal caregiving (Bridges et al., 1990). However, neither dopamine receptor agonism with the drugs bromocriptine or ergocornine, nor hypophysectomy, affects the onset or maintenance of maternal behaviors in naturally pregnant and parturient rats (Mann, Michael, & Svare, 1980; Numan, Leon, & Moltz, 1972; Rodriguez-Sierra & Rosenblatt, 1977). Peripartum pharmacological inhibition of pituitary PRL also does not affect maternal acceptance of nursing in parturient sheep (Poindron & Le Neindre, 1980). Such apparently inconstant findings are likely due to the fact that the major source of PRL during early pregnancy (and in non-pregnant females) is exclusively the anterior pituitary gland. During early pregnancy, PRL is secreted from the pituitary in twice-daily pulses that provide PRL to the brain and also to the ovarian corpora lutea to stimulate progesterone release necessary to maintain pregnancy. By mid-pregnancy, however, decidual luteotropins take over the progesterone-stimulating role, and hypophysectomy does not disrupt pregnancy. Furthermore, by this time the placentae have begun secreting their own lactogens (i.e., placental lactogens), which facilitate the onset of motherhood even in the absence of maternal pituitary PRL (Bridges et al., 1996). In fact, only when bromocriptine is given to rats or mice during the first few days of pregnancy, when the pituitary is still the source of PRL, is their later postpartum maternal behavior impaired (and this occurs only under stressful conditions) (Larsen & Grattan, 2010; Price & Bridges, 2014). The role of placental lactogens for establishing or maintaining maternal behaviors may differ among species, because PRL inhibition by dopamine receptor agonism does disrupt the onset of maternal behavior in hamsters when given on the day of parturition (McCarthy et al., 1994) as well as disrupts its maintenance when given chronically during lactation (Wise & Pryor, 1977). Furthermore, PRL inhibition negatively affects both the onset and maintenance of nest building and nursing when given during late pregnancy and/or early postpartum in rabbits (Gonzalez-Mariscal et al., 2000; Gonzalez-Mariscal et al., 2004).
The positive effects of PRL and placental lactogens on maternal care are centrally mediated. Relatively low doses of PRL, which cannot stimulate maternal behavior in ovarian steroid-primed virgin rats when given peripherally, are effective when given intracerebroventricularly (ICV) (Bridges et al., 1990). And even lower doses of PRL are capable of stimulating caregiving if infused directly into the mPOA (Bridges et al., 1996; Bridges et al., 1997). Placental lactogens infused into the mPOA also produce a rapid onset of maternal behavior in steroid-primed nulliparous rats (Bridges et al., 1996; Bridges et al., 1997), indicating the mPOA as a primary locus of action for PRL and related molecules for the onset of motherhood. PRL further acts in other places within the brain to affect maternal behavior, including by stimulating neurogenesis in the subventricular zone of the lateral ventricles during early pregnancy, from which those newborn cells migrate to the olfactory bulbs and elsewhere to alter maternal olfaction and affective responding in ways relevant for mothers’ behavior toward pups (Larsen & Grattan, 2012; Shingo et al., 2003).
There are two forms of the PRL receptor, long and short, that have similar extracellular domains but differ in their intracellular domains and function (Binart, Bachelot, & Bouilly, 2010). The long form of the PRL receptor is the best studied for a role in reproduction, and its expression or transcriptional activity is upregulated in female laboratory rodents by exogenous estradiol, late pregnancy, or lactation in some brain sites involved in maternal caregiving including the mPOA and hypothalamus (Bakowska & Morrell, 1997; Brown et al., 2017; Pi & Grattan, 1999). Nulliparous female mice that are homozygous for a lifelong, full-body knockout of the PRL receptor rarely retrieve pups during a maternal sensitization paradigm, and although their reproductively competent heterozygous sisters are maternal, they leave some pups scattered in their cage (Lucas et al., 1998).
More targeted work using female mice with pre-mating-induced viral vector-mediated knockout of PRL receptors only in the mPOA showed that they give birth normally and show typical parturitional grouping and cleaning of pups. Nonetheless, the females never showed maternal care thereafter and abandoned their nests (Brown et al., 2017). Consistent with these findings, chronic PRL receptor antagonism in the mPOA delays the onset of maternal behaviors in steroid-primed virgin rats (Bridges et al., 2001). Less dramatic effects of PRL receptor inhibition were found in a study where early postpartum rats were given five days of ICV antisense oligonucleotides targeting the PRL receptor, which resulted in somewhat delayed pup retrieval but otherwise mostly normal mothering (Torner et al., 2002).
The phenotypes of mPOA cells that are targeted by PRL to promote maternal caregiving are surely numerous and interactive. Female mice with conditional knockout of PRL receptors from GABA and/or glutmatergic cells in their brains have surprisingly intact postpartum maternal behavior. This could indicate that there is redundancy in the maternal behavior neural network in mice, and/or that other PRL-sensitive cell phenotypes in the mPOA are primarily involved. The first possibility is strongly suggested by research showing normal if not even faster maternal behavior in postpartum mice with neuronal elimination of STAT5 signaling, which is one of the major intracellular pathways involved in PRL receptor signaling (Buonfiglio et al., 2015). In addition, mice with PRL gene mutation, which cannot produce the peptide at all, are infertile but show normal spontaneous retrieval as virgins (Horseman et al., 1997). With regard to the second possibility, many dopamine-synthesizing cells within the mPOA and numerous nearby hypothalamic cells groups express PRL receptors (Brown et al., 2015; DeMaria et al., 1999). Some of these cells project within or to the mPOA and influence maternal caregiving via both D1 and D2 dopamine receptors (Miller & Lonstein, 2005, 2009; Numan et al., 2005), and these cells may be a PRL receptor target in the mPOA worthwhile exploring for a role in maternal caregiving.
Given how much literature there is on a positive role for PRL in non-human maternal behavior, the relationships among peripartum or postpartum PRL and maternal caregiving in women has been mostly ignored. Basal circulating PRL levels rise from mid-pregnancy to the final few weeks of pregnancy (Storey & Ziegler, 2016), and during the postpartum period spike in response to suckling or even other infant cues (e.g., cries). Pregnant women show elevated plasma PRL after being exposed to infant cries and other infant stimuli (Delahunty et al., 2007) and breastfeeding is associated with higher maternal sensitivity (Jonas & Woodside, 2016; Kim et al., 2011; Tharner et al., 2012). One study of 30 women showed that plasma PRL was uncorrelated with instrumental maternal activities with the infant when measured during the first few days postpartum (Fleming et al., 1987). In the only two studies of non-human primates, there were also no significant associations between plasma PRL and maternal behavior in lactating rhesus macaques (Maestripieri et al., 2009) or common marmosets (Saltzman & Abbott, 2005), although systemic bromocriptine eliminated or at least reduced infant carrying by parentally inexperienced females and male marmosets (Roberts et al., 2001). There are numerous polymorphisms in both the PRL and PRLR genes in women (Lee et al., 2007), but apparently no studies of a relationship between these gene variants and maternal caregiving have been conducted. This could be fruitful, as such associations between PRLR variants and caregiving have been found in female sheep (Wang et al., 2015).
Similar to PRL, the nonapeptide OT has also long been associated with peripherally occurring phenomena associated with maternity in mammals, in this case uterine muscle contractions at parturition and the ejection of milk from the mammary glands during lactation. Pedersen and Prange (1979) were the first to reveal that OT also had a central effect on maternal caregiving, with intracerebroventricular (ICV) infusion of OT compelling many gonadally intact or ovariectomized/estrogen-primed female rats to show maternal behavior within two hours after treatment (Pedersen & Prange, 1979; Pedersen et al., 1982). The presence of natural or exogenous estradiol is almost always necessary for OT’s pro-maternal effects because estradiol strongly upregulates OT receptors (OTRs) in a number of brain sites involved in motherhood (e.g., de Kloet et al., 1986; Johnson et al., 1989; Meddle et al., 2007). As already discussed, OT administration has also been seen to promote positive responses to young in female mice (McCarthy, 1990) and sheep (Kendrick, Keverne, & Baldwin, 1987; Levy et al., 1992).
Consistent with such effects, disrupting OTR activity by central infusion of an OTR antagonist can greatly disrupt the onset of maternal behaviors in estradiol-primed, pregnancy-terminated, or recently parturient rats (Fahrbach et al., 1985; Pedersen et al., 1985; van Leengoed, Kerker, & Swanson, 1987). OTR blockade in postpartum rats produces no gross disruption of their maternal behaviors but instead reduces maternal licking and nursing by a small-to-moderate degree (Bosch & Neumann, 2008; Champagne et al., 2001; Fahrbach et al., 1985; Pedersen & Boccia, 2003). Correlative evidence also indicates that OTR expression in the mPOA, hypothalamus, nucleus accumbens, and elsewhere in the brains of female rats, mice, and prairie voles is associated positively or even negatively with high maternal caregiving behaviors (Champagne et al., 2001; Olazabal & Young, 2006a, 2006b; Olazabal & Alsina-Llanes, 2016). These results collectively suggest that OT has greater relevance for the onset rather than the maintenance of motherhood. The source of OT for its neural effects on maternal behaviors is probably not the pituitary gland, because circulating plasma OT at physiological levels has no transporter mechanism that allows much of it to cross the blood-brain-barrier (Jurek & Neumann, 2018; Neumann et al., 2013). Instead, the relevant OT comes from cells in the hypothalamus and elsewhere that synthesize OT and release the peptide intracerebrally (Kelly & Goodson, 2014; Landgraf & Neumann, 2004). The mPOA and VTA are two targets of intracerebral OT’s facilitation of maternal caregiving in rats—repeated infusion of an OTR antagonist into either brain region during parturition disrupts retrieval and crouching over the litter (Pedersen et al., 1994). Furthermore, a functional MRI study in postpartum rats showed increased BOLD signal in many cortical and subcortical areas of the brain in response to suckling (or to central injection of OT), but that this BOLD activity was blunted in the mPOA and a few other sites when the suckled rats were given intracerebral OTR antagonists (Febo, Numan, & Ferris, 2005).
Some readers may be surprised to hear that the role of OT in even the onset of maternal behavior is somewhat equivocal, because while some laboratories also found a rapid onset of maternal behavior in female rats after central OT infusion (Fahrbach et al., 1984), others could not (Bolwerk & Swanson, 1984; Rubin, Menniti, & Bridges, 1983; Wamboldt & Insel, 1987). Experiments from Fahrbach, Morrell, and Pfaff (1986) suggested that methodological differences among studies in the females’ pre-test stress levels (specifically, their familiarity with the testing cage) determined their responsiveness to central OT infusion, such that only stressed rats respond to OT with a rapid onset of maternal behavior. This may be because one of OT’s many functions is to act as an anxiolytic (Jurek & Neumann, 2018; MacDonald & Feifel, 2014), and there is often an inverse relationship between females’ level of anxiety or fear and their propensity to act maternally (Fleming & Luebke, 1981; Lonstein, 2007). Even so, some female rats are not rapidly maternal after central OT infusion even when stressed (Wamboldt & Insel, 1987).
Studies of transgenic mice with disruption of the oxytocin gene (Oxt) or oxytocin receptor gene (Oxtr) further demonstrate that the OT system is not necessarily required for maternal caregiving. Constitutive lack of OT has surprisingly little effect on dams—parturition is normal, and no gross impairments in maternal behavior are found, although milk ejection is severely impaired (Nishimori et al., 1996; Young et al., 1996). Even so, a study of nulliparous mice of a strain that is already spontaneously maternal revealed through detailed behavioral observations that OT-knockout females on some test days were less likely than wildtype controls to retrieve all test pups to a corner of the test cage, showed ~25% less pup licking, but normal kyphotic nursing (Pedersen et al., 2006).
Studies of whole-body OTR-knockout mice have found that they can also give birth normally but do not lactate (Macbeth et al., 2010; Takayanagi et al. 2005). With regard to their behavior, one line of nulliparous and postpartum OTR-KO mice was found to be slower to retrieve pups and spend less time huddled over them (Takayanagi et al., 2005), but in another line the virgins showed typically high levels of maternal behavior toward pups (Macbeth et al., 2010). Perhaps not surprising, selective OTR-KO only in midbrain serotonin cells also does not disrupt maternal responding in this strain of nulliparous mice (Pagani et al., 2015). Interestingly, conditional OTR-KO mice with receptor loss only in the forebrain also show normal postpartum maternal behavior, but for an unknown reason these dams are more likely than wildtype dams to have some pups die within a few days after parturition (Macbeth et al., 2010). A later study by this same group involving whole-body OTR-KO mice also found that two-thirds of knockout dams lost their entire litters within 24 hours after parturition (the loss was not directly observed so its reason is unknown), but that the caregiving behavior of the knockout dams whose litters did survive was similar to wildtype controls (Rich et al., 2014). In sum, the consensus seems to be that under some circumstances, OT can facilitate the onset of caregiving but only has a modulatory role on the quality of particular maternal behaviors during the postpartum period in laboratory research animals. In both cases, OT signaling may do so by elevating animals’ threshold for fear- or anxiety-related responses to the neonates themselves or other anxiolytic stimuli associated with testing that interfere with their ability to positively respond to young (Yoshihara, Numan, & Kuroda, 2017).
In women, the role of OT in maternal caregiving is also mixed. Overall, OT concentration is high near the end of pregnancy when compared to non-pregnant controls (Altemus et al., 2004; Silber, Larsson, & Uvnas-Moberg, 1991). However, some work has found that OT increases across pregnancy (Dawood, Ylikorkala, & Trivedi, 1979; De Geest et al., 1985) while others found increases only in late pregnancy (Leake et al., 1981; Van der Post et al., 1997) or no increase (Feldman et al., 2007). These rises when found are suggested to buffer the emotionally distressing effects of adrenal stress hormones released during labor, and increase bonding and maternal caregiving behavior in the postpartum period (Carter, Altemus, & Pchrousos, 2001). OT levels in the postpartum period are seen to be generally higher than during pregnancy in most studies (Jobst et al., 2016; Van der Post et al., 1997), but not all (Feldman et al., 2007). In addition, OT levels vary widely in women (Feldman et al., 2007; Levine et al., 2007; Prevost et al., 2014) and in response to many factors. For example, low OT concentrations are associated with postpartum depression and depressive symptoms (Moura, Canavarro, & Figueiredo-Braga, 2016; Skrundz et al., 2011; Stuebe, Grewen, & Meltzer-Brody, 2013), and higher OT concentrations are associated with breastfeeding (Grewen, Davenport, & Light, 2010; Silber et al., 1991; Uvnäs-Moberg et al., 1990). A mother’s own relationship attachment experiences may also shape her OT patterns when postpartum (Eapen et al., 2014; Strathearn et al., 2009; Strathearn, 2011; Strathearn et al., 2012). Lower OT plasma concentrations were associated with more maternal avoidant attachment and attachment anxiety and deceases in self-reports of maternal infant bonding (Eapen et al., 2014). In other studies, maternal plasma OT levels rose in response to viewing their own infant’s faces (Strathearn et al., 2009) or interacting with their own infant (Strathearn, 2011), but only in mothers with a secure attachment history.
Generally, higher OT both pre- and postnatally is associated with more positive maternal caregiving behaviors in women (Feldman et al., 2007, Levine et al., 2007), but not in all studies (Elmadih et al., 2014). For instance, increases in OT across gestation were associated with self-reports of higher maternal-fetal attachment during pregnancy (Levine et al., 2007), while higher plasma OT in the postpartum period is associated with more affectionate maternal behaviors (Gordon et al., 2010; Levine et al., 2007) and maternal cognition attachment representations (Feldman et al., 2007). However, plasma OT was instead higher in low- sensitivity than high-sensitivity mothers in one study (Elmadih et al., 2014), from which the authors concluded that OT may be released particularly in these women to alleviate fear/stress as suggested by other work evaluating the role of OT on social stress in women (Taylor, Saphire-Bernstein, & Seeman, 2010; Turner et al., 2002). The maternal OT system also responds to infant cues. In a modified Still Face procedure, mothers who showed high OT response from baseline to infant interaction were able to sustain their gaze longer toward their infant during periods of distress relative to those with lower OT levels (Kim et al., 2014). In addition, higher positive mood was associated with a greater OT area under the curve in response to a bout of breastfeeding (Stuebe et al., 2013).
Single nucleotide polymorphism in the OXTR gene, such as A/G variation at rs53576 has also been associated with maternal sensitivity. Mothers with the GG genotype are less sensitive than mothers with the AA or AG genotypes in a series of problem solving tasks with their children (Bakermans-Kranenburg & van Ijzendoorn, 2008), regardless of depression status, income, age, or marital discord. Similar results were found in a study that analyzed both the role of polymorphisms for OTR and CD38 (Feldman et al., 2012), a glycoprotein involved in OT secretion (Jin et al., 2007). Less parental touch in a parent-child interaction and self-reports of parental care were associated with not only less plasma OT, but more OXTR rs2254298 TT and CD38 CC polymorphisms than OXTR polymorphism carrying the GG or GT allele or CD38 carrying the AA or AC allele. Three years ago, it was found that there was an OXT gene by environment interaction on maternal behavior (Mehta et al., 2016), with mothers having a higher predetermined OXT genetic risk score and separation anxiety showing less maternal sensitivity in a free play paradigm.
Studies have begun to suggest that theory of mind may explain the link between OT and maternal behavior (MacKinnon et al., 2014; MacKinnon et al., 2018). Mothers who performed well on a theory of mind task showed less intrusive maternal behaviors than mothers who performed poorly, and the effect was mediated by OT levels (MacKinnon et al., 2018). How these results may translate to behavioral interventions are unclear. Few studies have addressed the behavioral effects of OT administration on human maternal behavior and sensitivity, but one such study found that OT altered maternal responses to infants in mothers with postpartum depression. Following intranasal OT administration, women engaged in a play session with their infant and then listened to pre-recorded infant cries. There were no differences observed in maternal sensitivity, but mothers in the OT condition rated the recorded cries as more urgent than those in the placebo group. However, these mothers were also more likely to say they would choose a harsh caregiving response after listening to the cry (Mah et al., 2017). Given the small sample size, the clinical implications are difficult to determine, but this work is consistent with the idea that OT influences the emotional salience of cues, including in mothers (Elmadih et al., 2014; Feldman, Gordon, Zagoory-Sharon, 2011). This is suggested to occur either by promoting prosocial acts, attenuating stress, and/or regulating cooperation and conflict among groups (Shamay-Tsoory & Abu-Akel, 2016), all of which are involved in the performance of maternal behavior. However, it is important to note again that plasma OT levels do not necessarily reflect central OT levels (as reviewed in Jurek & Neumann, 2018) and, therefore, the data beyond the peripheral effects of OT should be interpreted with caution.
Closely related to OT is the nonapeptide arginine-vasopressin (AVP). The receptors for AVP are the V1a (mostly in the brain), V1b (brain and periphery), and V2 (mostly in the periphery), all of which belong to the family of G-protein-coupled receptors. The first evidence for a role of the AVP system in maternal caregiving emerged from studies in the 1980s where AVP was used as a control for infusions of OT (Pedersen & Prange, 1979; Pedersen et al., 1982). While centrally infused OT rapidly facilitated the onset of maternal care as discussed previously above (see section on oxytocin), AVP had a similar effect but with a delay in gonadally intact virgin rats (Pedersen & Prange, 1979) and in ovariectomized, estrogen-primed virgin rats (Pedersen et al., 1982). In confirmation, centrally infused anti-AVP antiserum in ovariectomized, primed virgin rats (Pedersen et al., 1985), as well as locally infused V1a receptor antagonist into the mPOA of lactating rats (Pedersen et al., 1994), delayed the onset of maternal care but did so to a lesser extent than the OT treatments. At the time, the AVP effects were interpreted as being mediated via OT receptors or maybe even vice versa given the fact that at higher doses these peptides can bind to one another’s receptors. For unclear reasons, research on OT’s role in maternal caregiving blossomed while research on AVP’s role essentially stopped. Nonetheless, there continued to be indications that the AVP system might be involved in maternal care, including that it becomes upregulated in the peripartum period (Caldwell et al., 1987; Landgraf et al., 1991; Lightman et al., 2001; Van Tol et al., 1988; Walker et al., 2001). For example, expression of AVP mRNA in the PVN (Bosch et al., 2007; Walker et al., 2001; Windle et al., 1997) and release of AVP within limbic areas of the brain (Landgraf et al., 1991) increase during lactation. Given the antidiuretic function of AVP, these results had mainly been interpreted as maintaining osmotic homeostasis during lactation (Caldwell et al., 1987; Landgraf et al., 1991; Walker et al., 2001).
By the late 2000s, the AVP system was finally demonstrated in rats and other species to be important regulator of maternal behavior, especially for maintaining the behavior (Kessler et al., 2011; Bester-Meredith & Marler, 2012). In lactating rats, chronic central infusion of AVP increased maternal care, whereas repeated infusions of a V1a or a V1b receptor antagonist decreased it (Bayerl et al., 2014; Bosch & Neumann, 2008). Furthermore, chronically stressed rat mothers show increased maternal care and faster pup retrieval when chronically infused with AVP centrally (Coverdill et al., 2012). The mPOA is a key brain region for AVP’s effects on maternal care; here V1a receptor binding is increased in lactation (Bosch & Neumann, 2008), and interacting with the pups triggers the release of AVP within the maternal mPOA (Bosch et al., 2010). Local activation of V1a receptors by AVP, or upregulating V1a receptor expression via an adeno-associated viral vector, facilitates maternal care while reducing the availability of V1a receptors by means of a V1a receptor antisense oligodeoxynucleotides impairs caregiving behaviors (Bosch & Neumann, 2008). Interestingly, reducing V1b receptors facilitates maternal retrieval of pups (Bayerl et al., 2016), suggesting that a higher expression level of V1a receptors is needed for pup retrieval in postpartum mothers (Bayerl et al., 2016).
In addition to maternal care, the display of maternal aggression is influenced by the AVP system. AVP-deficient Brattleboro lactating rats show impaired maternal aggression (Fodor et al., 2014), and in lactating rats bred for high (HAB) or low anxiety-related behavior (LAB) (Landgraf et al., 2007; Neumann et al., 2011), central infusion of a V1a receptor antagonist decreases the number of attacks in the initially more aggressive HAB dams whereas chronic central infusion of AVP increases attacks by the initially less aggressive LAB dams (Bosch & Neumann, 2012). Furthermore, the release of AVP within the central nucleus of the amygdala (CeA) (but not the PVN) increases during the display of maternal aggression in HAB dams (Bosch & Neumann, 2012). This is relevant because blocking V1a receptors locally in the CeA of HAB dams impairs maternal aggression whereas infusion of AVP in LAB dams promotes it. (Bosch & Neumann, 2010). Similar effects of aggression on AVP release, and V1a receptor blockade, are found in the BST of lactating rats (Bosch, 2013; Bosch et al., 2010). In contrast to these findings, some groups report that AVP might instead impair maternal aggression (Coverdill et al., 2012; Nephew & Bridges, 2008a, 2008b; Nephew, Byrnes, & Bridges, 2010). The contrasting findings are likely due to differences in the experimental design rather than in the different rat strains (i.e., Wistar versus Sprague-Dawley; Bosch & Neumann, 2012; Veenema & Neumann, 2008).
Corticotropin Releasing Factor
The brain CRF system consists of four polypeptidergic ligands (CRF and Urocortins (UCN) 1–3), CRF-binding protein that binds CRF and UCN1 to reduce their availability for the receptors, and two receptors (CRFR1 and CRFR2). The most prominent function of the brain CRF system is within the HPA axis, with CRF synthesized in neurons of the parvocellular PVN and released into the portal system of the adenohypophysis to stimulate ACTH release into the general circulation.
With respect to maternal caregiving, an initial study in ovariectomized, ovarian hormone-primed rats demonstrated that central infusion of CRF inhibits maternal behavior and induces pup killing (Pedersen et al., 1991), although the latter does not occur in postpartum CRF-treated rats (Klampfl, Neumann, & Bosch, 2013; Klampfl et al., 2014). This suggests that the CRF system needs to be downregulated postpartum in order for mothers to display proper maternal behavior. Indeed, CRF mRNA expression in the parvocellular part of the PVN is lower in lactating compared to nulliparous rats (Johnstone et al., 2000; Klampfl et al., 2013; Lightman et al., 2001; Walker et al., 2001) but see (da Costa et al., 2001; Deschamps, Woodside, & Walker, 2003), whereas CRF mRNA expression is higher during lactation in other brain sites including the BST (Klampfl et al., 2016a; Walker et al., 2001). The expression of CRF receptor mRNA appears to be independent of female reproductive status (Klampfl et al., 2014, 2016a). Depending on the brain region, however, one of the two CRF receptors has a more negative impact on maternal caregiving than the other receptor. For example, in the mPOA (Klampfl et al., 2018) and anterior-dorsal BST (Klampfl et al., 2014), activating CRF-R1s impairs maternal care and/or maternal aggression to a greater extent than does activating CRF-R2s. In the medial-posterior BST, the opposite effects are found (Klampfl et al., 2016a). Furthermore, CRF-R2 in the lateral septum is responsible for reduced maternal aggression in lactating mice (D’Anna & Gammie, 2009).
In addition, reducing the capacity of the CRF-binding protein (i.e., increasing the availability of CRF and UCN1) impairs maternal aggression in lactating mice (Gammie, Seasholtz, & Stevenson, 2008), whereas it increases it in lactating rats (Klampfl et al., 2016b). These opposite outcomes might be species differences or due to the different approaches used (genetic knock out in mice versus acute treatment in rats) (Klampfl et al., 2016b). In general, activity of the brain CRF system needs to be dampened in postpartum mothers to enable them to adequately express maternal care and aggression, independent of the species (D’Anna, Stevenson, & Gammie, 2005; D’Anna & Gammie, 2009; Gammie et al., 2004; Klampfl et al., 2013; Pedersen et al., 1991; Saltzman et al., 2011).
Other Peptide Hormones
Three other hypothalamic neuropeptides implicated in a number of motivated behaviors have also been linked to mothering and will be mentioned here. Orexin (OX), otherwise known as hypocretin, originates from the lateral and posterior hypothalamus, and its two forms (OX-A and OX-B) bind with differing affinities to the two orexin receptors (OX-1 and OX-2) (Tsujino & Sakurai, 2013). Pregnancy and early lactation produce inconsistent effects on hypothalamic OX immunoreactivity in laboratory rats (see Donlin et al., 2014), and other work shows that the more anteromedial OX populations are particularly malleable depending on lactation stage. For example, the OX cell populations increase then decrease in number from early to late lactation in response to regular suckling by the litter (Diniz et al., 2018; Donlin et al., 2014) suggesting particular relevance for maternal behaviors or lactation. Increasing central OX-A by ICV or mPOA infusion increases caregiving behaviors in early postpartum mice (D’Anna & Gammie, 2006) and late postpartum rats (Rivas et al., 2016), while OX-1 receptor antagonism in the mPOA at any time during lactation reduces retrieval and licking (but increases nursing) in rats (Rivas et al., 2016). There may be an inverted-U shaped relationship between mPOA orexin levels and caregiving, though, because postpartum females with the highest levels of endogenous mPOA orexin show the least contact with the litter (Grieb et al., 2017).
A flurry of studies in the past five years have also implicated galanin in maternal caregiving. Galanin is most highly expressed centrally in the hypothalamus and surrounding basal forebrain (Skofitsch & Jacobowitz, 1986), and is upregulated during natural or experimental increases in circulating estrogens (Bloch, Eckersell, & Mills, 1993; Faure-Virelizier et al., 1998; Vastagh & Liposits, 2017; Zhao et al., 2012). About one-third of galanin-synthesizing cells in the mPOA express Fos after rat or mouse dams display maternal behavior (Tsuneoka et al., 2013; Wu et al., 2014), and postpartum mice with ablated galanin-expressing cells in the mPOA do not retrieve pups. Nulliparous mice with their mPOA galanin-expressing cells ablated are more likely to attack pups than act maternally (Wu et al., 2014). Conversely, optogenetically stimulating galanin-expressing mPOA cells inhibit attacks on pups by virgin male mice and increase pup licking by experienced mouse fathers (Wu et al., 2014). Galanin-synthesizing cells in the mouse mPOA have efferent and afferent connections with many areas of the brain involved in sensory processing, endocrine function, and reward (Kohl et al., 2018). The subpopulation of these cells that show Fos expression in response to maternal behaviors have particularly dense projections to the midbrain periaqueductal gray and medial amygdala; the former population is particularly activated by pup licking while the latter population is more ubiquitously active when mothers interact with pups (Kohl et al., 2018). It is important to note that almost 10% of mPOA galanin-expressing cells, and almost 90% of them in the nearby anterior commissural nucleus, also synthesize OT (Cservenak et al., 2017). Many or most mPOA galanin-expressing cells also synthesize GABA (Sherin et al., 1998; Wu et al., 2014), and about half of the cells in the mPOA that are activated when female mice and rats display maternal behaviors are GABAergic (Lonstein & De Vries, 2000; Tsuneoka et al., 2013). Because of the co-localization between galanin and other neurochemicals, it is difficult to know if the effects of manipulating mPOA galanin-synthesizing cells on caregiving behaviors are due to the cells’ release of galanin or the other neurochemicals.
Melanin-concentrating hormone (MCH) is synthesized primarily by cells of the lateral hypothalamus and zona incerta, but unique populations of MCH-containing cells appear in the postpartum mPOA and PVN, which increase in number across mid-lactation and then declines as weaning approaches (Alvisi et al., 2016; Knollema et al., 1992; Rondini et al., 2010). Almost all MCH cells in the mPOA have the capacity to co-synthesize GABA (Rondini et al., 2010). Because the number of MCH cells in the mPOA of postpartum rats is positively correlated with litter size (Ferreira et al., 2017), it has been suggested that these cells are involved in suckling-induced metabolic changes in dams, the altered sleep patterns found in mothers, or the changes in maternal behavior that occur across lactation as the pups age (Benedetto, Torterolo, & Ferreiria, 2018). In support of its positive role in mothering behaviors, female mice with constitutive mutation of the MCH gene have greater pup mortality despite giving birth to normal-sized litters (Adams et al., 2011), and MCH1 receptor knockout dams display poorer nest building, slower retrieval of pups, and lower milk yield (Alachkar et al., 2016). On the other hand, Benedetto, Pereira, Ferreira and Torterolo (2014) found that infusing MCH into the early postpartum rat mPOA impaired retrieval and nesting, with a higher dose being particularly disruptive. The results of these studies may collectively indicate that too little or too much MCH signaling in the mPOA and elsewhere results in abnormal maternal caregiving.
The Nonhormonal Basis of Mothering
The decades of research already discussed have demonstrated the importance of steroid and peptide hormones in the onset and ongoing display of maternal care, as well as how remarkably conservative a role these factors play across mammalian species. As mentioned near the beginning of this article, while these endocrine and neuroendocrine factors promote a rapid positive response to infants by the time of parturition, they are not absolutely necessary for caregiving behavior in cases where nulliparous females are spontaneously maternal or able to become maternally sensitized after repeated exposure to unrelated pups. Thus, infants must be able to access the same neural substrates promoting caretaking that neuroendocrine hormones of pregnancy and parturition act upon in their absence. In support of this idea, recall that although the maternal brain is flooded with endocrine and neuroendocrine factors at birth, these circulating hormones quickly wane while caregiving behavior remains stable until offspring weaning. Further, multiparous animals are less reliant on hormonal fluctuations of birth to induce caregiving behavior. Thus, even the hormonal onset of maternal behavior must be maintained by hormone-independent mechanisms. Consideration of the cellular mechanisms of steroid hormone action may shed light on how the effects of hormone stimulation might persist long after steroids have cleared from circulation.
One mechanism through which steroid hormones exert their effects involves the activation of nuclear receptors, which interact with multi-protein complexes to modify chromatin and regulate the transcription of target genes (McKenna, 2015). Chromatin is the complex of DNA compactly coiled around histone proteins. Numerous post-translational modifications to histones such as acetylation, phosphorylation, and methylation can occur, and DNA itself can also be modified by methylation (Sweatt, 2009). The placement of epigenetic marks on the DNA and histones is regulated by the enzymatic activity of proteins such as histone acetyltransferases and methyltransferases and DNA methyltransferases. Histone marks can also be dynamically removed by histone deacetylases and demethylases. DNA methyl marks are also subject to dynamic, neural activity-dependent regulation, although the molecular mechanisms involved in demethylating DNA are less clear (Wu & Zhang, 2010). Thus, experience-dependent behavioral modifications might be facilitated by steroid hormone-driven alterations in transcriptional regulation (Frick et al., 2015). In the context of maternal care, one possibility is that chromatin modifications regulate genetic networks involved in the reorganization of the mPOA and other areas of the brain during initial mother–infant interactions (Stolzenberg & Champagne, 2016).
It is tempting to speculate that the neuroendocrine events of birth coordinate the transition to and maintenance of a maternal state through an epigenetic programming of gene expression in neural sites central to the regulation of care because these same molecular mechanisms could easily be accessed by repeated exposure to pups alone (Stolzenberg & Champagne, 2016). For example, estradiol stimulation regulates gene transcription through the ligand-driven activation of ERα and recruitment of the transcriptional coactivator and histone acetyltransferase, cyclic AMP response element binding protein (CREB) binding protein (CBP) (Bannister & Kouzarides, 1996; Ceschin et al., 2011; Edwards, 2000). CBP is also a coactivator of the transcription factor CREB (Kwok et al., 1994), a downstream target of cell surface signaling that is activated when virgin mice interact with pups, and found to be necessary for spontaneous maternal behavior (Jin, Blendy, & Thomas, 2005). Thus, the activation of CBP mediated histone acetylation may be one common molecular pathway through which either hormonal or experiential factors act to prime the maternal brain network.
From insemination to parturition and even beyond, the secretion of estrogens, progestins, glucocorticoids, lactogens, and a number of other peptide hormones act on the maternal brain to facilitate the willingness to accept, nurture, and protect offspring. Thus, the same physiological circumstances that act peripherally to enable the delivery and feeding of neonates also act centrally to strongly compel new mothers to positively respond to offspring cues and closely interact with their infants. While there are surely exceptions, the degree of conservation in the hormonal dynamics across pregnancy and the peripartum period that contribute to the onset of mothering in rodents, rabbits, sheep, and both human and some non-human primates is quite remarkable.
Despite the plethora of information gathered over the years regarding the endocrine and neuroendocrine control of motherhood, several pressing questions remain. For instance, although progesterone contributes to the hormonal priming of maternal care earlier in pregnancy, the specific locations and intracellular mechanisms through which it produces this effect are entirely unknown. Similarly, how progesterone shifts from being pro-maternal to anti-maternal, allowing its withdrawal to synchronize delivery with the onset of mothering, remains to be elucidated. Furthermore, PRL and placental lactogens are vital contributors to the ovarian steroid-induced onset of mothering, yet little is known about the role of lactogenic hormones on caregiving in humans or other primates. And despite the tremendous amount of research focusing on the role of OT in stimulating the onset of maternal behavior and its relationship to the nuances of postpartum maternal behaviors, still not much is known about its mechanism of action across the many brain sites where its receptor is induced by ovarian steroid priming. One interesting new idea is that OT might be involved in tuning sensory systems to infant cues, by regulating sensory plasticity in a top-down fashion (Oettl et al., 2016). Finally, in a number of mammalian models used to study maternal care, hormonal stimulation is rapid and sufficient, but not invariably required for caregiving behaviors to be expressed. In these cases, the neural mechanisms through which infants elicit their own nurturance is not only relevant for their mothers but also in other circumstances where potential parents do not undergo the dramatic endocrine and neuroendocrine fluctuations of pregnancy and parturition, such as fathers as well as related or unrelated alloparents.
Adams, A. C., Domouzoglou, E. M., Chee, M. J., Segal-Lieberman, G., Pissios, P., & Maratos-Flier, E. (2011). Ablation of the hypothalamic neuropeptide melanin concentrating hormone is associated with behavioral abnormalities that reflect impaired olfactory integration. Behavioural Brain Research, 224(1), 195–200.Find this resource:
Ahdieh, H. B., Mayer, A. D., & Rosenblatt, J. S. (1987). Effects of brain antiestrogen implants on maternal behavior and on postpartum estrus in pregnant rats. Neuroendocrinology, 46(6), 522–531.Find this resource:
Alachkar, A., Alhassen, L., Wang, Z., Wang, L., Onouye, K., Sanathara, N., & Civelli, O. (2016). Inactivation of the melanin concentrating hormone system impairs maternal behavior. European Neuropsychopharmacology, 26(11), 1826–1835.Find this resource:
Albrecht, E. D., & Pepe, G. J. (1990). Placental steroid hormone biosynthesis in primate pregnancy. Endocrine Reviews, 11(1), 124–150.Find this resource:
Albrecht, E. D., Haskins, A. L., & Pepe, G. J. (1980). The influence of fetectomy at midgestation upon the serum concentrations of progesterone, estrone, and estradiol in baboons. Endocrinology, 107(3), 766–770.Find this resource:
Altemus, M., Fong, J., Yang, R., Damast, S., Luine, V., & Ferguson, D. (2004). Changes in cerebrospinal fluid neurochemistry during pregnancy. Biological Psychiatry, 56(6), 386–392.Find this resource:
Alvisi, R. D., Diniz, G. B., Da-Silva, J. M., Bittencourt, J. C., & Felicio, L. F. (2016). Suckling-induced Fos activation and melanin-concentrating hormone immunoreactivity during late lactation. Life Sciences, 148, 241–246.Find this resource:
Angelier, F., Wingfield, J. C., Tartu, S., & Chastel, O. (2016). Does prolactin mediate parental and life-history decisions in response to environmental conditions in birds? A review. Hormones and Behavior, 77, 18–29.Find this resource:
Atkinson, H. C., & Waddell, B. J. (1995). The hypothalamic-pituitary-adrenal axis in rat pregnancy and lactation: Circadian variation and interrelationship of plasma adrenocorticotropin and corticosterone. Endocrinology, 136(2), 512–520.Find this resource:
Bahr, N. I., Martin, R. D., & Pryce, C. R. (2001). Peripartum sex steroid profiles and endocrine correlates of postpartum maternal behavior in captive gorillas (Gorilla gorilla gorilla). Hormones and Behavior, 40(4), 533–541.Find this resource:
Bakermans-Kranenburg, M. J., & van Ijzendoorn, M. H. (2008). Oxytocin receptor (OXTR) and serotonin transporter (5-HTT) genes associated with observed parenting. Social Cognitive and Affective Neuroscience, 3(2), 128–134.Find this resource:
Bakowska, J. C., & Morrell, J. I. (1997). Atlas of the neurons that express mRNA for the long form of the prolactin receptor in the forebrain of the female rat. The Journal of Comparative Neurology, 386(2), 161–177.Find this resource:
Bales, K. L., & Saltzman, W. (2016). Fathering in rodents: Neurobiological substrates and consequences for offspring. Hormones Behavior, 77, 249–259.Find this resource:
Bannister, A. J., & Kouzarides, T. (1996). The CBP co-activator is a histone acetyltransferase. Nature, 384(6610), 641.Find this resource:
Bardi, M., French, J. A., Ramirez, S. M., & Brent, L. (2004). The role of the endocrine system in baboon maternal behavior. Biological Psychiatry, 55(7), 724–732.Find this resource:
Bardi, M., et al. (2003). Peripartum sex steroid changes and maternal style in rhesus and Japanese macaques. General and Comparative Endocrinology, 133(3), 323–331.Find this resource:
Bardi, M., Shimizu, K., Fujita, S., Borgognini-Tarli, S., & Huffman, M. A. (2001). Hormonal correlates of maternal style in captive macaques (Macaca fuscata and M. mulatta). International Journal of Primatology, 22(4), 647–662.Find this resource:
Barrett, J., & Fleming, A. S. (2011). Annual research review: All mothers are not created equal: Neural and psychobiological perspectives on mothering and the importance of individual differences. Journal of Child Psychology and Psychiatry, 52(4), 368–397.Find this resource:
Basurto, E., Hoffman, K., Lemus, A. C., & González-Mariscal, G. (2018). Electrolytic lesions to the anterior hypothalamus-preoptic area disrupt maternal nest-building in intact and ovariectomized, steroid-treated rabbits. Hormones and Behavior, 102, 48–54.Find this resource:
Baum, M. J. (1978). Failure of pituitary transplants to facilitate the onset of maternal behavior in ovariectomized virgin rats. Physiology & Behavior, 20(1), 87–89.Find this resource:
Bayerl, D. S., Kaczmarek, V., Jurek, B., van den Burg, E. H., Neumann, I. D., Gaßner, B. M., . . . & Bosch, O. J. (2016). Antagonism of V1b receptors promotes maternal motivation to retrieve pups in the MPOA and impairs pup-directed behavior during maternal defense in the mpBNST of lactating rats. Hormones and Behavior, 79, 18–27.Find this resource:
Bayerl, D. S., Klampfl, S. M., & Bosch, O. J. (2014). Central V1b receptor antagonism in lactating rats: Impairment of maternal care but not of maternal aggression. Journal of Neuroendocrinology, 26(12), 918–926.Find this resource:
Beach, F. A., & Wilson, J. R. (1963). Effects of prolactin, progesterone and estrogen on reactions of nonpregnant rats to foster young. Psychological Reports, 13(1), 231–239.Find this resource:
Beehner, J. C., Nguyen, N., Wango, E. O., Alberts, S. C., & Altmann, J. (2006). The endocrinology of pregnancy and fetal loss in wild baboons. Hormones and Behavior, 49(5), 688–699.Find this resource:
Bellem, A. C., Monfort, S. L., & Goodrowe, K. L. (1995). Monitoring reproductive development, menstrual cyclicity, and pregnancy in the lowland gorilla (gorilla gorilla) by enzyme immunoassay. Journal of Zoo and Wildlife Medicine, 24–31.Find this resource:
Benedetto, L., Pereira, M., Ferreira, A., & Torterolo, P. (2014). Melanin-concentrating hormone in the medial preoptic area reduces active components of maternal behavior in rats. Peptides, 58, 20-25.Find this resource:
Benedetto, L., Torterolo, P., & Ferreira, A. (2018). Melanin-concentrating hormone: Role in nursing and sleep in mother rats. In Melanin-Concentrating Hormone and Sleep. Cham, Switzerland: Springer.Find this resource:
Bester-Meredith, J. K., & Marler, C. A. (2012). Naturally occurring variation in vasopressin immunoreactivity is associated with maternal behavior in female Peromyscus mice. Brain Behavior and Evolution, 80(4), 244–253.Find this resource:
Binart, N., Bachelot, A., & Bouilly, J. (2010). Impact of prolactin receptor isoforms on reproduction. Trends in Endocrinology & Metabolism, 21(6), 362–368.Find this resource:
Biswas, A., Dale, S. L., Gajewski, A., Nuzzo, P., & Chattoraj, S. C. (1991). Temporal relationships among the excretory patterns of 2-hydroxyestrone, estrone, estradiol, and progesterone during pregnancy in the rat. Steroids, 56(3), 136–141.Find this resource:
Blaustein, J. D., & Wade, G. N. (1977). Concurrent inhibition of sexual behavior, but not brain [–3H] estradiol uptake, by progesterone in female rats. Journal of Comparative and Physiological Psychology, 91(4), 742–751.Find this resource:
Bloch, G. J., Eckersell, C., & Mills, R. (1993). Distribution of galanin-immunoreactive cells within sexually dimorphic components of the medial preoptic area of the male and female rat. Brain Research, 620(2), 259–268.Find this resource:
Bolwerk, E. L., & Swanson, H. H. (1984). Does oxytocin play a role in the onset of maternal behaviour in the rat? The Journal of Endocrinology, 101(3), 353–357.Find this resource:
Bosch, O. J. (2013). Maternal aggression in rodents: Brain oxytocin and vasopressin mediate pup defence. Philosophical Transactions of the Royal Society B Biological Sciences, 368(1631), 20130085.Find this resource:
Bosch, O. J., & Neumann, I. D. (2008). Brain vasopressin is an important regulator of maternal behavior independent of dams’ trait anxiety. Proceedings of the National Academy of Sciences of the United States of America, 105(44), 17139–17144.Find this resource:
Bosch, O. J., & Neumann, I. D. (2010). Vasopressin released within the central amygdala promotes maternal aggression. European Journal of Neuroscience, 31(5), 883–891.Find this resource:
Bosch, O. J., Müsch, W., Bredewold, R., Slattery, D. A., & Neumann, I. D. (2007). Prenatal stress increases HPA axis activity and impairs maternal care in lactating female offspring: Implications for postpartum mood disorder. Psychoneuroendocrinology, 32(3), 267–278.Find this resource:
Bosch, O. J., Pförtsch, J., Beiderbeck, D. I., Landgraf, R., & Neumann, I. D. (2010). Maternal behaviour is associated with vasopressin release in the medial preoptic area and bed nucleus of the stria terminalis in the rat. Journal of Neuroendocrinology, 22(5), 420–429.Find this resource:
Bosch, O. J. (2011). Maternal nurturing is dependent on her innate anxiety: The behavioral roles of brain oxytocin and vasopressin. Hormones and Behavior, 59(2), 202–212.Find this resource:
Bosch, O. J., & Neumann, I. D. (2012). Both oxytocin and vasopressin are mediators of maternal care and aggression in rodents: From central release to sites of action. Hormones and Behavior, 61(3), 293–303.Find this resource:
Bowers, K., Ding, L., Gregory, S., Yolton, K., Ji, H., Meyer, J., . . . & Folger, A. (2018). Maternal distress and hair cortisol in pregnancy among women with elevated adverse childhood experiences. Psychoneuroendocrinology, 95, 145–148.Find this resource:
Bridges, R., Rigero, B. A., Byrnes, E. M., Yang, L., & Walker, A. M. (2001). Central infusions of the recombinant human prolactin receptor antagonist, S179D-PRL, delay the onset of maternal behavior in steroid-primed, nulliparous female rats. Endocrinology, 142(2), 730–739.Find this resource:
Bridges, R. S., Rosenblatt, J. S., & Feder, H. H. (1978). Serum progesterone concentrations and maternal behavior in rats after pregnancy termination: Behavioral stimulation after progesterone withdrawal and inhibition by progesterone maintenance. Endocrinology, 102(1), 258–267.Find this resource:
Bridges, R. S., Zarrow, M. X., Goldman, B. D., & Denenberg, V. H. (1974). A developmental study of maternal responsiveness in the rat. Physiology & Behavior, 12(1), 149–151.Find this resource:
Bridges, R. S., DiBiase, R., Loundes, D. D., & Doherty, P. C. (1985). Prolactin stimulation of maternal behavior in female rats. Science, 227(4688), 782–784.Find this resource:
Bridges, R. S., Numan, M., Ronsheim, P. M., Mann, P. E., & Lupini, C. E. (1990). Central prolactin infusions stimulate maternal behavior in steroid-treated, nulliparous female rats. Proceedings of the National Academy of Sciences of the United States of America, 87(20), 8003–8007.Find this resource:
Bridges, R. S., Robertson, M. C., Shiu, R. P., Sturgis, J. D., Henriquez, B. M., & Mann, P. E. (1997). Central lactogenic regulation of maternal behavior in rats: Steroid dependence, hormone specificity, and behavioral potencies of rat prolactin and rat placental lactogen I. Endocrinology, 138(2), 756–763.Find this resource:
Bridges, R. S., Robertson, M. C., Shiu, R. P., Friesen, H. G., Stuer, A. M., & Mann, P. E. (1996). Endocrine communication between conceptus and mother: Placental lactogen stimulation of maternal behavior. Neuroendocrinology, 64(1), 57–64.Find this resource:
Bridges, R. S. (1984). A quantitative analysis of the roles of dosage, sequence, and duration of estradiol and progesterone exposure in the regulation of maternal behavior in the rat. Endocrinology, 114(3), 930–940.Find this resource:
Bridges, R. S. (2015). Neuroendocrine regulation of maternal behavior. Frontiers in Neuroendocrinology, 36, 178–196.Find this resource:
Bridges, R. S., & Scanlan, V. F. (2005). Maternal memory in adult, nulliparous rats: Effects of testing interval on the retention of maternal behavior. Developmental Psychobiology, 46(1), 13–18.Find this resource:
Brown, R. S., Herbison, A. E., & Grattan, D. R. (2015). Effects of Prolactin and Lactation on A15 Dopamine neurones in the rostral preoptic area of female mice. Journal of Neuroendocrinology, 27(9), 708–717.Find this resource:
Brown, R. S. E., Aoki, M., Ladyman, S. R., Phillipps, H. R., Wyatt, A., Boehm, U., & Grattan, D. R. (2017). Prolactin action in the medial preoptic area is necessary for postpartum maternal nursing behavior. Proceedings of the National Academy of Sciences of the United States of America, 114(40), 10779–10784.Find this resource:
Brummelte, S., Pawluski, J. L., & Galea, L. A. M. (2006). High post-partum levels of corticosterone given to dams influence postnatal hippocampal cell proliferation and behavior of offspring: A model of post-partum stress and possible depression. Hormones and Behavior, 50(3), 370–382.Find this resource:
Brunelli, S. A., Shindledecker, R. D., & Hofer, M. A. (1985). Development of maternal behaviors in prepubertal rats at three ages: Age-characteristic patterns of responses. Developmental Psychobiology, 18(4), 309–326.Find this resource:
Brunton, P. J., & Russell, J. A. (2011). Neuroendocrine control of maternal stress responses and fetal programming by stress in pregnancy. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 35(5), 1178–1191.Find this resource:
Buonfiglio, D. C., Ramos-Lobo, A. M., Silveira, M. A., Furigo, I. C., Hennighausen, L., Frazão, R., & Donato, J., Jr. (2015). Neuronal STAT5 signaling is required for maintaining lactation but not for postpartum maternal behaviors in mice. Hormones and Behavior, 71, 60–68.Find this resource:
Burriss, R. P., Little, A. C., & Nelson, E. C. (2007). 2D:4D and sexually dimorphic facial characteristics. Archives of Sexual Behavior, 36(3), 377–384.Find this resource:
Caldwell, J. D., Greer, R., Johnson, M. F., Prange, A. J., Jr., & Pedersen, C. A. (1987). Oxytocin and vasopressin immunoreactivity in hypothalamic and extrahypothalamic sites in late pregnant and postpartum rats. Neuroendocrinology, 46(1), 39–47.Find this resource:
Campbell, E. A., Linton, E. A., Wolfe, C. D. A., Scraggs, P. R., Jones, M. T., & Lowry, P. J. (1987). Plasma corticotropin-releasing hormone concentrations during pregnancy and parturition. The Journal of Clinical Endocrinology & Metabolism, 64(5), 1054–1059.Find this resource:
Caparros-Gonzalez, R. A., Romero-Gonzalez, B., Strivens-Vilchez, H., Gonzalez-Perez, R., Martinez-Augustin, O., & Peralta-Ramirez, M. I. (2017). Hair cortisol levels, psychological stress and psychopathological symptoms as predictors of postpartum depression. PloS one, 12(8), e0182817.Find this resource:
Carnegie S. D., Fedigan L. M., & Ziegler T. E. (2011). Social and environmental factors affecting fecal glucocorticoids in wild, female white-faced capuchins (Cebus capucinus). American Journal of Primatology, 73(9), 861–869.Find this resource:
Carr, B. R., Parker, C. R., Madden, J. D., MacDonald, P. C., & Porter, J. C. (1981). Maternal plasma adrenocorticotropin and cortisol relationships throughout human pregnancy. American Journal of Obstetrics and Gynecology, 139(4), 416–422.Find this resource:
Carter, C. S., Altemus, M., & Pchrousos, G. (2001). Chapter 17 Neuroendocrine and emotional changes in the post-partum period. Progress in Brain Research, 133, 241–249.Find this resource:
Caughey, S. D., Klampfl, S. M., Bishop, V. R., Pfoertsch, J., Neumann, I. D., Bosch, O. J., & Meddle, S. L. (2011). Changes in the intensity of maternal aggression and central oxytocin and vasopressin V1a receptors across the peripartum period in the rat. Journal of Neuroendocrinology, 23(11), 1113–1124.Find this resource:
Ceschin, D. G., Walia, M., Wenk, S. S., Duboé, C., Gaudon, C., Xiao, Y., . . . Gronemeyer, H. (2011). Methylation specifies distinct estrogen-induced binding site repertoires of CBP to chromatin. Genes & Development, 25(11), 1132–1146.Find this resource:
Challis, J. R., Davies, J., & Ryan, K. J. (1973). The concentrations of progesterone, estrone and estradiol-17 beta in the plasma of pregnant rabbits. Endocrinology, 93(4), 971–976.Find this resource:
Chamley, W. A., Buckmaster, J. M., Cerini, M. E., Cumming, I. A., Goding, J. R., Obst, J. M., . . . Winfield, C. (1973). Changes in the levels of progesterone, corticosteroids, estrone, estradiol-17 β, luteinizing hormone, and prolactin in the peripheral plasma of the ewe during late pregnancy and at parturition. Biology of Reproduction, 9(1), 30–35.Find this resource:
Champagne, F., Diorio, J., Sharma, S., & Meaney, M. J. (2001). Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors. Proceedings of the National Academy of Sciences of the United States of the America, 98(22), 12736–12741.Find this resource:
Champagne, F. A., Francis, D. D., Mar, A., & Meaney, M. J. (2003). Variations in maternal care in the rat as a mediating influence for the effects of environment on development. Physiology & Behavior, 79(3), 359–371.Find this resource:
Champagne, F. A., Curley, J. P., Keverne, E. B., & Bateson, P. P. G. (2007). Natural variations in postpartum maternal care in inbred and outbred mice. Physiology & Behavior, 91(2–3), 325–334.Find this resource:
Cockburn, A. (2006). Prevalence of different modes of parental care in birds. Proceedings of the Royal Society B Biological Sciences, 273(1592), 1375–1383.Find this resource:
Cohen, M., Stiefel, M., Reddy, W. J., & Laidlaw, J. C. (1958). (1958). The secretion and disposition of cortisol during pregnancy. Journal of Clinical Endocrinology and Metabolism, 18(10), 1076–1092.Find this resource:
Conde, A., & Figueiredo, B. (2014). 24-h urinary free cortisol from mid-pregnancy to 3-months postpartum: Gender and parity differences and effects. Psychoneuroendocrinology, 50, 264–273.Find this resource:
Connor, J. R., & Davis, H. N. (1980a). Postpartum estrus in Norway rats. II. Physiology. Biology of Reproduction, 23(5), 1000–1006.Find this resource:
Connor, J. R., & Davis, H. N. (1980b). Postpartum estrus in Norway rats. I. Behavior. Biology of Reproduction, 23(5), 994–999.Find this resource:
Coverdill, A. J., McCarthy, M., Bridges, R. S., & Nephew, B. C. (2012). Effects of chronic Central Arginine Vasopressin (AVP) on maternal behavior in chronically stressed rat dams. Brain Sciences, 2(4).Find this resource:
Crump, M. L. (1996). Parental care among the Amphibia. In J. S. Rosenblatt & C.T. Snowdon (Eds.), Advances in the study of behavior (pp. 109–144). New York, NY: Academic Press.Find this resource:
Cservenak, M., Kis, V., Keller, D., Dimen, D., Menyhart, L., Olah, S., . . . Dobolyi, A. (2017). Maternally involved galanin neurons in the preoptic area of the rat. Brain Struct Funct, 222(2), 781–798.Find this resource:
Czekala, N. M., Benirschke, K., McClure, H., & Lasley, B. L. (1983). Urinary estrogen excretion during pregnancy in the gorilla (Gorilla gorilla), orangutan (Pongo pygmaeus) and the human (Homo sapiens). Biology of Reproduction, 28(2), 289–294.Find this resource:
D’Anna, K. L., & Gammie, S. C. (2006). Hypocretin-1 dose-dependently modulates maternal behaviour in mice. Journal of Neuroendocrinology, 18(8), 553–566.Find this resource:
D’Anna, K. L., & Gammie, S. C. (2009). Activation of corticotropin-releasing factor receptor 2 in lateral septum negatively regulates maternal defense. Behavioral Neuroscience, 123(2), 356–368.Find this resource:
D’Anna, K. L., Stevenson, S. A., & Gammie, S. C. (2005). Urocortin 1 and 3 impair maternal defense behavior in mice. Behavioral Neuroscience, 119(4), 1061–1071.Find this resource:
D’Anna-Hernandez, K. L., Ross, R. G., Natvig, C. L., & Laudenslager, M. L. (2011). Hair cortisol levels as a retrospective marker of hypothalamic–pituitary axis activity throughout pregnancy: Comparison to salivary cortisol. Physiology & Behavior, 104(2), 348–353.Find this resource:
D’Anna-Hernandez, K. L., Hoffman, M. C., Zerbe, G. O., Coussons-Read, M., Ross, R. G., & Laudenslager, M. L. (2012). Acculturation, maternal cortisol, and birth outcomes in women of Mexican descent. Psychosomatic Medicine, 74(3), 296–304.Find this resource:
da Costa, A. P., Ma, X., Ingram, C. D., Lightman, S. L., & Aguilera, G. (2001). Hypothalamic and amygdaloid corticotropin-releasing hormone (CRH) and CRH receptor-1 mRNA expression in the stress-hyporesponsive late pregnant and early lactating rat. Brain Research. Molecular Brain Research, 91(1–2), 119–130.Find this resource:
Da Costa, A. P. C., Guevara‐Guzman, R. G., Ohkura, S., Goode, J. A., & Kendrick, K. M. (1996). The role of oxytocin release in the paraventricular nucleus in the control of maternal behaviour in the sheep. Journal of Neuroendocrinology, 8(3), 163–177.Find this resource:
Darne, J., McGarrigle, H. H., & Lachelin, G. C. (1987). Saliva oestriol, oestradiol, oestrone and progesterone levels in pregnancy: Spontaneous labour at term is preceded by a rise in the saliva oestriol:progesterone ratio. British Journal of Obstetrices and Gynaecology, 94(3), 227–235.Find this resource:
Dawood, M. Y., Ylikorkala, O., & Trivedi, D. (1979). Oxytocin in maternal circulation and amniotic fluid during pregnancy. The Journal of Clinical Endocrinology & Metabolism, 49(3), 429–434.Find this resource:
De Geest, K., Thiery, M., Piron-Possuyt, G., & Driessche, R. V. (1985). Plasma oxytocin in human pregnancy and parturition. Journal of Perinatal Medicine-Official Journal of the WAPM, 13(1), 3–14.Find this resource:
de Kloet, E. R., Voorhuis, D. A., Boschma, Y., & Elands, J. (1986). Estradiol modulates density of putative ‘oxytocin receptors’ in discrete rat brain regions. Neuroendocrinology, 44(4), 415–421.Find this resource:
De Lauzon, S., Uhrich, F., Vandel, S., Cittanova, N., & Jayle, M. F. (1974). Determination of progesterone and of free and conjugated estrogens in pregnant and pseudo-pregnant rats. Steroids, 24(1), 31–40.Find this resource:
de Sousa, F. L., Lazzari, V., de Azevedo, M. S., de Almeida, S., Sanvitto, G. L., Lucion, A. B., & Giovenardi, M. (2010). Progesterone and maternal aggressive behavior in rats,” Behavioural Brain Research, 212(1), 84–89.Find this resource:
Delahunty, K. M., McKay, D. W., Noseworthy, D. E., & Storey, A. E. (2007). Prolactin responses to infant cues in men and women: Effects of parental experience and recent infant contact. Hormones and Behavior, 51(2), 213–220.Find this resource:
DeMaria, J. E., Lerant, A. A., & Freeman, M. E. (1999). Prolactin activates all three populations of hypothalamic neuroendocrine dopaminergic neurons in ovariectomized rats. Brain Research, 837(1–2), 236–241.Find this resource:
Deschamps, S., Woodside, B., & Walker, C. D. (2003). Pups presence eliminates the stress hyporesponsiveness of early lactating females to a psychological stress representing a threat to the pups. Journal of Neuroendocrinology, 15(5), 486–497.Find this resource:
Dewsbury, D. A. (1990). Modes of estrus induction as a factor in studies of the reproductive behavior of rodents. Neuroscience & Biobehavioral Reviews, 14(2), 147–155.Find this resource:
Diaz, S., Cardenas, H., Zepeda, A., Brandeis, A., Schiappacasse, V., Miranda, P., . . . Croxatto, H. B. (1995). Luteinizing hormone pulsatile release and the length of lactational amenorrhoea. Human Reproduction, 10(8), 1957–1961.Find this resource:
Diniz, G. B., Candido, P. L., Klein, M. O., Alvisi, R. D., Presse, F., Nahon, J. L., . . . Bittencourt, J. C. (2018). The weaning period promotes alterations in the orexin neuronal population of rats in a suckling-dependent manner. Brain Structure and Function.Find this resource:
Doerr, H. K., Siegel, H. I., & Rosenblatt, J. S. (1981). Effects of progesterone withdrawal and estrogen on maternal behavior in nulliparous rats. Behavioral and Neural Biology, 32(1), 35–44.Find this resource:
Donlin, M., Cavanaugh, B. L., Spagnuolo, O. S., Yan, L., & Lonstein, J. S. (2014). Effects of sex and reproductive experience on the number of orexin A-immunoreactive cells in the prairie vole brain. Peptides, 57, 122–128.Find this resource:
Dulac, C., & Wagner, S. (2006). Genetic analysis of brain circuits underlying pheromone signaling. Annu. Rev. Genet., 40, 449–467.Find this resource:
Dupont, S., Krust, A., Gansmuller, A., Dierich, A., Chambon, P., & Mark, M. (2000). Effect of single and compound knockouts of estrogen receptors alpha (ERalpha) and beta (ERbeta) on mouse reproductive phenotypes. Development, 127(19), 4277–4291.Find this resource:
Eapen, V., Dadds, M., Barnett, B., Kohlhoff, J., Khan, F., Radom, N., & Silove, D. M. (2014). Separation anxiety, attachment and inter-personal representations: Disentangling the role of oxytocin in the perinatal period. PloS One, 9(9), e107745.Find this resource:
Edwards, D. P. (2000). The role of coactivators and corepressors in the biology and mechanism of action of steroid hormone receptors. Journal of Mammary Gland Biology and Neoplasia, 5(3), 307–324.Find this resource:
Edwards, P. D., & Boonstra, R. (2017). Glucocorticoids and CBG during pregnancy in mammals: Diversity, pattern, and function. General and Comparative Endocrinology, 259, 122–130.Find this resource:
Elmadih, A., Wan, M. W., Numan, M., Elliott, R., Downey, D., & Abel, K. M. (2014). Does oxytocin modulate variation in maternal caregiving in healthy new mothers? Brain Research, 1580, 143–150.Find this resource:
Fahrbach, S. E., Morrell, J. I., & Pfaff, D. W. (1984). Oxytocin induction of short-latency maternal behavior in nulliparous, estrogen-primed female rats. Hormones and Behavior, 18(3), 267–286.Find this resource:
Fahrbach, S. E., Morrell, J. I., & Pfaff, D. W. (1985). Possible role for endogenous oxytocin in estrogen-facilitated maternal behavior in rats. Neuroendocrinology, 40(6), 526–532.Find this resource:
Fahrbach, S. E., Morrell, J. I., & Pfaff, D. W. (1986). Effect of varying the duration of pre-test cage habituation on oxytocin induction of short-latency maternal behavior. Physiology & behavior, 37(1), 135–139.Find this resource:
Fahrbach, S. E., & Pfaff, D. W. (1986). Effect of preoptic region implants of dilute estradiol on the maternal behavior of ovariectomized, nulliparous rats. Hormones and Behavior, 20(3), 354–363.Find this resource:
Fang, Y. Y., Yamaguchi, T., Song, S. C., Tritsch, N. X., & Lin, D. (2018). A hypothalamic midbrain pathway essential for driving maternal behaviors. Neuron, 98(1), 192–207.e10.Find this resource:
Faure-Virelizier, C., Croix, D., Bouret, S., Prevot, V., Reig, S., Beauvillain, J. C., & Mitchell, V. (1998). Effects of estrous cyclicity on the expression of the galanin receptor Gal-R1 in the rat preoptic area: A comparison with the male. Endocrinology, 139(10), 4127–4139.Find this resource:
Febo, M., Numan, M., & Ferris, C. F. (2005). Functional magnetic resonance imaging shows oxytocin activates brain regions associated with mother-pup bonding during suckling. Journal of Neuroscience, 25(50), 11637–11644.Find this resource:
Feldman, R., Gordon, I., & Zagoory‐Sharon, O. (2011). Maternal and paternal plasma, salivary, and urinary oxytocin and parent–infant synchrony: Considering stress and affiliation components of human bonding. Developmental Science, 14(4), 752–761.Find this resource:
Feldman, R., Weller, A., Zagoory-Sharon, O., & Levine, A. (2007). Evidence for a neuroendocrinological foundation of human affiliation: Plasma oxytocin levels across pregnancy and the postpartum period predict mother-infant bonding. Psychological Science, 18(11), 965–970.Find this resource:
Feldman, R., Zagoory-Sharon, O., Weisman, O., Schneiderman, I., Gordon, I., Maoz, R., . . . Ebstein, R. P. (2012). Sensitive parenting is associated with plasma oxytocin and polymorphisms in the OXTR and CD38 genes. Biological Psychiatry, 72(3), 175–181.Find this resource:
Felton, T. M., Linton, L. N., Rosenblatt, J. S., & Morrell, J. I. (1999). Estrogen implants in the lateral habenular nucleus do not stimulate the onset of maternal behavior in female rats. Hormones and Behavior, 35(1), 71–80.Find this resource:
Fernandez-Duque, E., Valeggia, C. R., & Mendoza, S. P. (2009). The biology of paternal care in human and nonhuman primates. Annual Review of Anthropology, 38, 115–130.Find this resource:
Ferreira, J. G. P., Duarte, J. C. G., Diniz, G. B., & Bittencourt, J. C. (2017). Litter size determines the number of melanin-concentrating hormone neurons in the medial preoptic area of Sprague Dawley lactating dams. Physiology & Behavior, 181, 75–79.Find this resource:
Finegood, E. D., Blair, C., Granger, D. A., Hibel, L. C., Mills-Koonce, R., & The Family Life Project Key, Investigators. (2016). Psychobiological influences on maternal sensitivity in the context of adversity. Developmental Psychology, 52(7), 1073–1087.Find this resource:
Fite, J. E., & French, J. A. (2000). Pre- and postpartum sex steroids in female marmosets (Callithrix kuhlii): Is there a link with infant survivorship and maternal behavior? Hormones and Behavior, 38(1), 1–12.Find this resource:
Fleming, A. S., & Luebke, C. (1981). Timidity prevents the virgin female rat from being a good mother: Emotionality differences between nulliparous and parturient females. Physiology & Behavior, 27(5), 863–868.Find this resource:
Fleming, A. S., Steiner, M., & Anderson, V. (1987). Hormonal and attitudinal correlates of maternal behaviour during the early postpartum period in first-time mothers. Journal of Reproductive and Infant Psychology, 5, 193–205.Find this resource:
Fleming, A. S., & Rosenblatt, J. S. (1974). Maternal behavior in the virgin and lactating rat. Journal of Comparative and Physiological Psychology, 86(5), 957.Find this resource:
Fleming, A. S., & Sarker, J. (1990). Experience-hormone interactions and maternal behavior in rats. Physiology & Behavior, 47(6), 1165–1173.Find this resource:
Fleming, A. S., Steiner, M., & Corter, C. (1997a), Cortisol, hedonics, and maternal responsiveness in human mothers. Hormones and Behavior, 32(2), 85–98.Find this resource:
Fleming, A. S., Ruble, D., Krieger, H., & Wong, P. Y. (1997b). Hormonal and experiential correlates of maternal responsiveness during pregnancy and the puerperium in human mothers. Hormones and Behavior, 31(2), 145–158.Find this resource:
Fodor, A., Barsvari, B., Aliczki, M., Balogh, Z., Zelena, D., Goldberg, S. R., & Haller, J. (2014). The effects of vasopressin deficiency on aggression and impulsiveness in male and female rats. Psychoneuroendocrinology, 47, 141–150.Find this resource:
Francis, K., Meddle, S. L., Bishop, V. R., & Russell, J. A. (2002). Progesterone receptor expression in the pregnant and parturient rat hypothalamus and brainstem. Brain Research, 927(1), 18–26.Find this resource:
French, J. A., Koban, T., Rukstalis, M., Ramirez, S. M., Bardi, M., & Brent, L. (2004). Excretion of urinary steroids in pre- and postpartum female baboons. General and Comparative Endocrinology, 137(1), 69–77.Find this resource:
Frick, K. M., Kim, J., Tuscher, J. J., & Fortress, A. M. (2015). Sex steroid hormones matter for learning and memory: Estrogenic regulation of hippocampal function in male and female rodents. Learning & Memory, 22(9), 472–493.Find this resource:
Frodi, A. M., Murray, A. D., Lamb, M. E., & Steinberg, J. (1984). Biological and social determinants of responsiveness to infants in 10-to-15-year-old girls. Sex Roles, 10(7–8), 639–649.Find this resource:
Gadsby, J. E., Keyes, P. L., & Bill, C. H. (1983). Control of corpus luteum function in the pregnant rabbit: Role of estrogen and lack of a direct luteotropic role of the placenta. Endocrinology, 113(6), 2255–2262.Find this resource:
Gammie, S. C., Seasholtz, A. F., & Stevenson, S. A. (2008). Deletion of corticotropin-releasing factor binding protein selectively impairs maternal, but not intermale aggression. Neuroscience, 157(3), 502–512.Find this resource:
Gammie, S. C., Negron, A., Newman, S. M., & Rhodes, J. S. (2004). Corticotropin-releasing factor inhibits maternal aggression in mice. Behavioral Neuroscience, 118(4), 805–814.Find this resource:
Gans, C. (1996). An overview of parental care among the Reptilia. In J. S. Rosenblatt & C.T. Snowdon (Eds.), Advances in the study of behavior (pp. 115–139). New York, NY: Academic Press.Find this resource:
Gibori, G., & Sridaran, R. (1981). Sites of androgen and estradiol production in the second half of pregnancy in the rat. Biol Reprod, 24(2), 249–256.Find this resource:
Giesbrecht, G. F, Poole, J. C., Letourneau, N., Campbell, T., Kaplan, B. J., & Team, APrON Study. (2013). The buffering effect of social support on hypothalamic-pituitary-adrenal axis function during pregnancy. Psychosomatic Medicine, 75(9), 856–862.Find this resource:
Gillespie, S. L., Mitchell, A. M., Kowalsky, J. M., & Christian, L. M. (2018). Maternal parity and perinatal cortisol adaptation: The role of pregnancy-specific distress and implications for postpartum mood. Psychoneuroendocrinology, 97, 86–93.Find this resource:
Glynn, L. M., Davis, E. P., Sandman, C. A., & Goldberg, W. A. (2016). Gestational hormone profiles predict human maternal behavior at 1-year postpartum. Hormones and Behavior, 85, 19–25.Find this resource:
Glynn, L. M., & Sandman, C. A. (2012). Sex moderates associations between prenatal glucocorticoid exposure and human fetal neurological development. Developmental Science, 15(5), 601–610.Find this resource:
Glynn, L. M., Davis, E. P., & Sandman, C. A. (2013). New insights into the role of perinatal HPA-axis dysregulation in postpartum depression. Neuropeptides, 47(6), 363–370.Find this resource:
Glynn, L. M., Schetter, C. D., Chicz-DeMet, A., Hobel, C. J., & Sandman, C. A. (2007). Ethnic differences in adrenocorticotropic hormone, cortisol and corticotropin-releasing hormone during pregnancy. Peptides, 28(6), 1155–1161.Find this resource:
Gonzalez, A., Jenkins, J. M., Steiner, M., & Fleming, A. S. (2012). Maternal early life experiences and parenting: The mediating role of Cortisol and executive function. Journal of the American Academy of Child and Adolescent Psychiatry, 51(7), 673–682.Find this resource:
González-Mariscal, G., Díaz-Sánchez, V., Melo, A. I., Beyer, C., & Rosenblatt, J. S. (1994). Maternal behavior in New Zealand white rabbits: Quantification of somatic events, motor patterns, and steroid plasma levels. Physiology & Behavior, 55(6), 1081–1089.Find this resource:
González-Mariscal, G., Caba, M., Martínez-Gómez, M., Bautista, A., & Hudson, R. (2016). Mothers and offspring: The rabbit as a model system in the study of mammalian maternal behavior and sibling interactions. Hormones and Behavior, 77, 30–41.Find this resource:
Gonzalez-Mariscal, G., Chirino, R., Beyer, C., & Rosenblatt, J. S. (2004). Removal of the accessory olfactory bulbs promotes maternal behavior in virgin rabbits. Behavioural Brain Research, 152(1), 89–95.Find this resource:
Gonzalez-Mariscal, G., Melo, A. I., Jimenez, P., Beyer, C., & Rosenblatt, J. S. (1996). Estradiol, progesterone, and prolactin regulate maternal nest-building in rabbits. Journal of Neuroendocrinology, 8(12), 901–907.Find this resource:
Gonzalez-Mariscal, G., Melo, A. I., Parlow, A. F., Beyer, C., & Rosenblatt, J. S. (2000). Pharmacological evidence that prolactin acts from late gestation to promote maternal behaviour in rabbits. Journal of Neuroendocrinology, 12(10), 983–992.Find this resource:
González-Mariscal, G., Chirino, R., Rosenblatt, J. S., & Beyer, C. (2005). Forebrain implants of estradiol stimulate maternal nest-building in ovariectomized rabbits. Hormones and Behavior, 47(3), 272–279.Find this resource:
González‐Mariscal, G., Toribio, A., Gallegos, J. A., & Serrano‐Meneses, M. A. (2013). Characteristics of suckling stimulation determine the daily duration of mother‐young contact and milk output in rabbits. Developmental Psychobiology, 55(8), 809–817.Find this resource:
Goodwin, T. M. (1999). A role for estriol in human labor, term and preterm. Am J Obstet Gynecol, 180 (1 Pt 3), S208–213.Find this resource:
Gordon, I., Zagoory-Sharon, O., Leckman, J. F., & Feldman, R. (2010). Oxytocin and the development of parenting in humans. Biological Psychiatry, 68(4), 377–382.Find this resource:
Greco, B., Lubbers, L. S., & Blaustein, J. D. (2003). Estrogen receptor beta messenger ribonucleic acid expression in the forebrain of proestrous, pregnant, and lactating female rats. Endocrinology, 144(5), 1869–1875.Find this resource:
Grewen, K. M., Davenport, R. E., & Light, K. C. (2010). An investigation of plasma and salivary oxytocin responses in breast- and formula- feeding mothers of infants. Psychophysiology, 47(4), 625–632.Find this resource:
Grieb, Z. A., Tierney, S. M., & Lonstein, J. S. (2017). Postpartum inhibition of ovarian steroid action increases aspects of maternal caregiving and reduces medial preoptic area progesterone receptor expression in female rats. Hormones and Behavior, 96, 31–41.Find this resource:
Groer, M. W., & Morgan, K. (2007). Immune, health and endocrine characteristics of depressed postpartum mothers. Psychoneuroendocrinology, 32(2), 133–139.Find this resource:
Grota, L. J., & Ader, R. (1969). Continuous recording of maternal behaviour in Rattus norvegicus. Animal Behaviour, 17(4), 722–729.Find this resource:
Grota, L. J., & Ader, R. (1974). Behavior of lactating rats in a dual-chambered maternity cage. Hormones and Behavior, 5(4), 275–282.Find this resource:
Guerra-Araiza, C., Miranda-Martinez, A., Neri-Gómez, T., & Camacho-Arroyo, I. (2008). Sex steroids effects on the content of GAD, TH, GABA A, and glutamate receptors in the olfactory bulb of the male rat. Neurochemical Research, 33(8), 1568–1573.Find this resource:
Handley, S., Dunn, T., Waldron, G., & Baker, J. (1980). Tryptophan, cortisol and puerperal mood. British Journal of Psychiatry, 136(5), 498–508.Find this resource:
Hansen, S., Sodersten, P., & Eneroth, P. (1983). Mechanisms regulating hormone release and the duration of dioestrus in the lactating rat. The Journal of Endocrinology, 99(2), 173–180.Find this resource:
Hart, L. L., & Davie, J. R. (2002). The estrogen receptor: More than the average transcription factor. Biochemistry and Cell Biology, 80(3), 335–341.Find this resource:
Hennessy, M. B., Harney, K. S., Smotherman, W. P., Coyle, S., & Levine, S. (1977). Adrenalectomy-induced deficits in maternal retrieval in the rat. Hormones and Behavior, 9(3), 222–227.Find this resource:
Hoffman, M. C., Mazzoni, S. E., Wagner, B. D., Laudenslager, M. L., & Ross, R. G. (2016). Measures of maternal stress and mood in relation to preterm birth. Obstetrics and Gynecology, 127(3), 545–552.Find this resource:
Hopper, B. R., Tullner, W. W., & Gray, C. W. (1968). Urinary estrogen excretion during pregnancy in a gorilla (Gorilla gorilla). Proc Soc Exp Biol Med, 129(1), 213–214.Find this resource:
Horseman, N. D., Zhao, W., Montecino-Rodriguez, E., Tanaka, M., Nakashima, K., Engle, S. J., . . . Dorshkind, K. (1997). Defective mammopoiesis, but normal hematopoiesis, in mice with a targeted disruption of the prolactin gene. EMBO J, 16(23), 6926–6935.Find this resource:
Hrdy, S. B. (1977). Infanticide as a primate reproductive strategy. American Scientist, 65(1), 40–49.Find this resource:
Hudson, R., & Distel, H. (1982). The pattern of behaviour of rabbit pups in the nest. Behaviour, 79, 255–271.Find this resource:
Jarcho, M. R., Mendoza, S. P., & Bales, K. L. (2012). Hormonal and experiential predictors of infant survivorship and maternal behavior in a monogamous primate (Callicebus cupreus). American Journal of Primatology, 74(5), 462–470.Find this resource:
Jin, D., Liu, H. X., Hirai, H., Torashima, T., Nagai, T., Lopatina, O., . . . Higashida, H. (2007). CD38 is critical for social behaviour by regulating oxytocin secretion. Nature, 446, 41.Find this resource:
Jin, S. H., Blendy, J. A., & Thomas, S. A. (2005). Cyclic AMP response element-binding protein is required for normal maternal nurturing behavior. Neuroscience, 133(3), 647–655.Find this resource:
Jobst, A., Krause, D., Maiwald, C., Härtl, K., Myint, A. M., Kästner, R., . . . Weidinger, E. (2016). Oxytocin course over pregnancy and postpartum period and the association with postpartum depressive symptoms. Archives of Women’s Mental Health, 19(4), 571–579.Find this resource:
Johnson, A. E., Ball, G. F., Coirini, H., Harbaugh, C. R., McEwen, B. S., & Insel, T. R. (1989). Time course of the estradiol-dependent induction of oxytocin receptor binding in the ventromedial hypothalamic nucleus of the rat. Endocrinology, 125(3), 1414–1419.Find this resource:
Johnstone, H. A., Wigger, A., Douglas, A. J., Neumann, I. D., Landgraf, R., Seckl, J. R., & Russell, J. A. (2000). Attenuation of hypothalamic-pituitary-adrenal axis stress responses in late pregnancy: Changes in feedforward and feedback mechanisms. Journal of Neuroendocrinology, 12(8), 811–822.Find this resource:
Jonas, W., & Woodside, B. (2016). Physiological mechanisms, behavioral and psychological factors influencing the transfer of milk from mothers to their young. Hormones and Behavior, 77, 167–181.Find this resource:
Jung, C., Ho, J. T., Torpy, D. J., Rogers, A., Doogue, M., Lewis, J. G., . . . Inder, W. J. (2011). A longitudinal study of plasma and urinary cortisol in pregnancy and postpartum. The Journal of Clinical Endocrinology & Metabolism, 96(5), 1533–1540.Find this resource:
Jurek, B., & Neumann, I. D. (2018). The oxytocin receptor: From intracellular signaling to behavior. Physiological Reviews, 98(3), 1805–1908.Find this resource:
Juul, S. H., Hendrix, C., Robinson, B., Stowe, Z. N., Newport, D. J., Brennan, P. A., & Johnson, K. C. (2016) Maternal early-life trauma and affective parenting style: The mediating role of HPA-axis function. Archives of Women’s Mental Health, 19(1), 17–23.Find this resource:
Kalra, S., Einarson, A., Karaskov, T., Van Uum, S., & Koren, G. (2007). The relationship between stress and hair cortisol in healthy pregnant women. Clinical & Investigative Medicine, 30(2), 103–107.Find this resource:
Keller, M., Meurisse, M., & Lévy, F. (2004a). Mapping the neural substrates involved in maternal responsiveness and lamb olfactory memory in parturient ewes using Fos imaging. Behavioral Neuroscience, 118(6), 1274.Find this resource:
Keller, M., Perrin, G., Meurisse, M., Ferreira, G., & Lévy, F. (2004b). Cortical and medial amygdala are both involved in the formation of olfactory offspring memory in sheep. European Journal of Neuroscience, 20(12), 3433–3441.Find this resource:
Kelly, A. M., & Goodson, J. L. (2014). Social functions of individual vasopressin-oxytocin cell groups in vertebrates: What do we really know? Front Neuroendocrinol, 35(4), 512–529.Find this resource:
Kendrick, K. M., Keverne, E. B., & Baldwin, B. A. (1987). Intracerebroventricular oxytocin stimulates maternal behaviour in the sheep. Neuroendocrinology, 46(1), 56–61.Find this resource:
Kendrick, K. M., Levy, F., & Keverne, E. B. (1991). Importance of vaginocervical stimulation for the formation of maternal bonding in primiparous and multiparous parturient ewes. Physiology & Behavior, 50(3), 595–600.Find this resource:
Kendrick, K. M., Levy, F., & Keverne, E. B. (1992a). Changes in the sensory processing of olfactory signals induced by birth in sleep. Science, 256(5058), 833–836.Find this resource:
Kendrick, K. M., et al. (1992b). Oxytocin, amino acid and monoamine release in the region of the medial preoptic area and bed nucleus of the stria terminalis of the sheep during parturition and suckling. Brain Research, 569(2), 199–209.Find this resource:
Keresztes, P., Ayers, J. W., Menon, K. M., & Romani, T. (1988). Comparison of peripheral, uterine and cord estrogen and progesterone levels in laboring and nonlaboring women at term. The Journal of Reproductive Medicine, 33(8), 691–694.Find this resource:
Kessler, M. S., Bosch, O. J., Bunck, M., Landgraf, R., & Neumann, I. D. (2011). Maternal care differs in mice bred for high vs. low trait anxiety: Impact of brain vasopressin and cross-fostering. Social Neuroscience, 6(2), 156–168.Find this resource:
Kim, P., Feldman, R., Mayes, L. C., Eicher, V., Thompson, N., Leckman, J. F., & Swain, J. E. (2011). Breastfeeding, brain activation to own infant cry, and maternal sensitivity. Journal of Child Psychology and Psychiatry, and allied disciplines, 52(8), 907–915.Find this resource:
Kim, S., Fonagy, P., Koos, O., Dorsett, K., & Strathearn, L. (2014). Maternal oxytocin response predicts mother-to-infant gaze. Brain Research, 1580, 133–142.Find this resource:
Kirschbaum, C., Tietze, A., Skoluda, N., & Dettenborn, L. (2009). Hair as a retrospective calendar of cortisol production—increased cortisol incorporation into hair in the third trimester of pregnancy. Psychoneuroendocrinology, 34(1), 32–37.Find this resource:
Kivlighan, K., Dipietro, J. A., Costigan, K. A., & Laudenslager, M. L. (2008). Diurnal rhythm of cortisol during late pregnancy: Associations with maternal psychological well-being and fetal growth. Psychoneuroendocrinology, 33, 1225–1235.Find this resource:
Klampfl, S. M., Neumann, I. D., & Bosch, O. J. (2013). Reduced brain corticotropin-releasing factor receptor activation is required for adequate maternal care and maternal aggression in lactating rats. European Journal of Neuroscience, 38(5), 2742–2750.Find this resource:
Klampfl, S. M., Brunton, P. J., Bayerl, D. S., & Bosch, O. J. (2014). Hypoactivation of CRF receptors, predominantly type 2, in the medial-posterior BNST is vital for adequate maternal behavior in lactating rats. The Journal of Neuroscience, 34(29), 9665–9676.Find this resource:
Klampfl, S. M., Brunton, P. J., Bayerl, D. S., & Bosch, O. J. (2016a). CRF-R1 activation in the anterior-dorsal BNST induces maternal neglect in lactating rats via an HPA axis-independent central mechanism. Psychoneuroendocrinology, 64, 89–98.Find this resource:
Klampfl, S. M., Schramm, M. M., Stinnett, G. S., Bayerl, D. S., Seasholtz, A. F., & Bosch, O. J. (2016b). Brain CRF-binding protein modulates aspects of maternal behavior under stressful conditions and supports a hypo-anxious state in lactating rats. Hormones and Behavior, 84, 136–144.Find this resource:
Klampfl, S. M., Schramm, M. M., Gassner, B. M., Hubner, K., Seasholtz, A. F., Brunton, P. J., . . . Bosch, O. J. (2018). Maternal stress and the MPOA: Activation of CRF receptor 1 impairs maternal behavior and triggers local oxytocin release in lactating rats. Neuropharmacology, 133, 440–450.Find this resource:
Kleiman, D. G. (1977). Monogamy in mammals. Q Rev Biol, 52(1), 39–69.Find this resource:
Knollema, S., Brown, E. R., Vale, W., & Sawchenko, P. E. (1992). Novel hypothalamic and preoptic sites of prepro-melanin-concentrating hormone messenger ribonucleic Acid and Peptide expression in lactating rats. Journal of Neuroendocrinology, 4(6), 709–717.Find this resource:
Koch, M., & Ehret, G. (1989). Immunocytochemical localization and quantitation of estrogen-binding cells in the male and female (virgin, pregnant, lactating) mouse brain. Brain Research, 489(1), 101–112.Find this resource:
Kohl, J., Babayan, B. M., Rubinstein, N. D., Autry, A. E., Marin-Rodriguez, B., Kapoor, V., . . . Dulac, C. (2018). Functional circuit architecture underlying parental behavior. Nature, 556(7701), 326–331.Find this resource:
Korach, K. S. (1994). Insights from the study of animals lacking functional estrogen receptor. Science, 266(5190), 1524–1527.Find this resource:
Krpan, K. M., Coombs, R., Zinga, D., Steiner, M., & Fleming, A. S. (2005). Experiential and hormonal correlates of maternal behavior in teen and adult mothers. Hormones and Behavior, 47(1), 112–122.Find this resource:
Kuroda, K. O., & Tsuneoka, Y. (2013). Assessing postpartum maternal care, alloparental behavior, and infanticide in mice: With notes on chemosensory influences. In Pheromone Signaling (pp. 331–347). Totowa, NJ: Humana Press.Find this resource:
Kwok, R., Lundblad, James R, Chrivia, John C, Richards, Jane P, Bächinger, Hans Peter, Brennan, Richard G, . . . Goodman, Richard H. (1994). Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature, 370(6486), 223.Find this resource:
Landgraf, R., & Neumann, I. D. (2004); Vasopressin and oxytocin release within the brain: A dynamic concept of multiple and variable modes of neuropeptide communication. Front Neuroendocrinol, 25(3–4), 150–176.Find this resource:
Landgraf, R., Neumann, I., & Pittman, Q. J. (1991). Septal and hippocampal release of vasopressin and oxytocin during late pregnancy and parturition in the rat. Neuroendocrinology, 54(4), 378–383.Find this resource:
Landgraf, R., Kessler, M. S., Bunck, M., Murgatroyd, C., Spengler, D., Zimbelmann, M., . . . Frank, E. (2007). Candidate genes of anxiety-related behavior in HAB/LAB rats and mice: Focus on vasopressin and glyoxalase-I. Neuroscience & Biobehavioral Reviews, 31(1), 89–102.Find this resource:
Larsen, C. M., & Grattan, D. R. (2010). Prolactin-induced mitogenesis in the subventricular zone of the maternal brain during early pregnancy is essential for normal postpartum behavioral responses in the mother. Endocrinology, 151(8), 3805–3814.Find this resource:
Larsen, C. M., & Grattan, D. R. (2012). Prolactin, neurogenesis, and maternal behaviors. Brain Behav Immun, 26(2), 201–209.Find this resource:
Law Smith, M. J., Deady, D. K., Moore, F. R., Jones, B. C., Cornwell, R. E., Stirrat, M., . . . Perrett, D. I. (2012). Maternal tendencies in women are associated with estrogen levels and facial femininity. Hormones and Behavior, 61(1), 12–16.Find this resource:
Le Neindre, P., Poindron, P., & Delouis, C. (1979). Hormonal induction of maternal behavior in non-pregnant ewes. Physiology & Behavior, 22(4), 731–734.Find this resource:
Leake, R. D., Weitzman, R. E., Glatz, T. H., & Fisher, D. A. (1981). Plasma oxytocin concentrations in men, nonpregnant womesn, and pregnant women before and during spontaneous labor. The Journal of Clinical Endocrinology & Metabolism, 53(4), 730–733.Find this resource:
Lee, S. A., Haiman, C. A., Burtt, N. P., Pooler, L. C., Cheng, I., Kolonel, L. N., . . . Stram, D. O. (2007). A comprehensive analysis of common genetic variation in prolactin (PRL) and PRL receptor (PRLR) genes in relation to plasma prolactin levels and breast cancer risk: The multiethnic cohort. BMC Medical Genetics, 8, 72.Find this resource:
Lehrman, D. S. (1955). The physiological basis of parental feeding behavior in the ring dove (Streptopelia risoria). Behaviour, 7(4), 241–286.Find this resource:
Leon, M., Numan, M., & Chan, A. (1975). Adrenal inhibition of maternal behavior in virgin female rats. Hormones and Behavior, 6(2), 165–171.Find this resource:
Levine, A., et al. (2007). Oxytocin during pregnancy and early postpartum: Individual patterns and maternal–fetal attachment. Peptides, 28(6), 1162–1169.Find this resource:
Levy, F., et al. (1997). Scopolamine impairs the ability of parturient ewes to learn to recognise their lambs. Psychopharmacology, 129(1), 85–90.Find this resource:
Levy, F., Gervais, R., Kindermann, U., Orgeur, P., & Piketty, V. (1990). Importance of! b-noradrenergic receptors in the olfactory bulb of sheep for recognition of lambs. Behavioral Neuroscience, 104(3), 464–469.Find this resource:
Lévy, F., Locatelli, A., Piketty, V., Tillet, Y., & Poindron, P. (1995). Involvement of the main but not the accessory olfactory system in maternal behavior of primiparous and multiparous ewes. Physiology & Behavior, 57(1), 97–104.Find this resource:
Levy, F., Kendrick, K. M., Keverne, E. B., Piketty, V., & Poindron, P. (1992). Intracerebral oxytocin is important for the onset of maternal behavior in inexperienced ewes delivered under peridural anesthesia. Behavioral Neuroscience, 106(2), 427–432.Find this resource:
Liggins, G. C. (1994). The role of cortisol in preparing the fetus for birth. Reproduction, Fertility and Development, 6(2), 141–150.Find this resource:
Lightman, S. L., Windle, R. J., Wood, S. A., Kershaw, Y. M., Shanks, N., & Ingram, C. D. (2001). Peripartum plasticity within the hypothalamo-pituitary-adrenal axis. Progress in Brain Research, 133, 111–129.Find this resource:
Linton, E., Perkins, A., & Woods, R. (1993). Corticotropin-releasing hormone-binding protein (CRH-BP): Plasma levels decrease during the third trimester of normal human pregnancy. Journal of Clinical Endocrinology and Metabolism, 76, 260–262.Find this resource:
Löfgren, M., Bäckström, T., & Torbjörn, M. (1997). High progesterone is related to effective human labor: Study of serum progesterone and 5α-pregnane-3, 20-dione in normal and abnormal deliveries. Acta obstetricia et gynecologica Scandinavica, 76(5), 423–430.Find this resource:
Lonstein, J. S. (2007). Regulation of anxiety during the postpartum period. Front Neuroendocrinol, 28(2–3), 115–141.Find this resource:
Lonstein, J. S., & De Vries, G. J. (2000). Maternal behaviour in lactating rats stimulates c-fos in glutamate decarboxylase-synthesizing neurons of the medial preoptic area, ventral bed nucleus of the stria terminalis, and ventrocaudal periaqueductal gray. Neuroscience, 100(3), 557–568.Find this resource:
Lonstein, J. S., & Fleming, A. S. (2002). Parental behaviors in rats and mice. Current Protocols in Neuroscience, Chapter 8, Unit 8 15.Find this resource:
Lonstein, J. S., & Gammie, S. C. (2002). Sensory, hormonal, and neural control of maternal aggression in laboratory rodents. Neuroscience & Biobehavioral Reviews, 26(8), 869–888.Find this resource:
Lonstein, J. S., Simmons, D. A., & Stern, J. M. (1998). Functions of the caudal periaqueductal gray in lactating rats: Kyphosis, lordosis, maternal aggression, and fearfulness. Behavioral Neuroscience, 112(6), 1502.Find this resource:
Lonstein, J. S., Wagner, C. K., & De Vries, G. (1999). Comparison of the ‘nursing’ and other parental behaviors of nulliparous and lactating female rats. Hormones and Behavior, 36(3), 242–251.Find this resource:
Lonstein, J. S., Maguire, J., Meinlschmidt, G., & Neumann, I. D. (2014). Emotion and mood adaptations in the peripartum female: Complementary contributions of GABA and oxytocin. Journal of Neuroendocrinology, 26(10), 649–664.Find this resource:
Lott, D. F., & Fuchs, S. S. (1962). Failure to induce retrieving by sensitization or injection of prolactin. Journal of Comparative and Physiological Psychology, 55(6), 1111–1113.Find this resource:
Lucas, B. K., Ormandy, C. J., Binart, N., Bridges, R. S., & Kelly, P. A. (1998). Null mutation of the prolactin receptor gene produces a defect in maternal behavior. Endocrinology, 139(10), 4102–4107.Find this resource:
Luisi, S., Luisi, S., Petraglia, F., Benedetto, C., Nappi, R. E., Bernardi, F., Fadalti, M., . . . Genazzani, A. R. (2000). Serum allopregnanolone levels in pregnant women: Changes during pregnancy, at delivery, and in hypertensive patients. The Journal of Clinical Endocrinology & Metabolism, 85(7), 2429–2433.Find this resource:
Macbeth, A. H., Stepp, J. E., Lee, H. J., Young, W. S., III, & Caldwell, H. K. (2010). Normal maternal behavior, but increased pup mortality, in conditional oxytocin receptor knockout females. Behavioral Neuroscience, 124(5), 677–685.Find this resource:
MacDonald, K., & Feifel, D. (2014). Oxytocin’s role in anxiety: A critical appraisal. Brain Research, 1580, 22–56.Find this resource:
MacKinnon, A. L., Gold, I., Feeley, N., Hayton, B., Carter, C. S., & Zelkowitz, P. (2014). The role of oxytocin in mothers’ theory of mind and interactive behavior during the perinatal period. Psychoneuroendocrinology, 48, 52–63.Find this resource:
MacKinnon, A. L., Carter, C. S., Feeley, N., Gold, I., Hayton, B., Santhakumaran, S., & Zelkowitz, P. (2018). Theory of mind as a link between oxytocin and maternal behaviour. Psychoneuroendocrinology, 92, 87–94.Find this resource:
Maestripieri, D., & Wallen, K. (1995). Interest in infants varies with reproductive condition in group-living female pigtail macaques (Macaca nemestrina). Physiology & Behavior, 57(2), 353–358.Find this resource:
Maestripieri, D., & Zehr, J. L. (1998). Maternal responsiveness increases during pregnancy and after estrogen treatment in macaques. Hormones and Behavior, 34(3), 223–230.Find this resource:
Maestripieri, D., & Pelka, S. (2002). Sex differences in interest in infants across the lifespan - A biological adaptation for parenting? Human Nature-an Interdisciplinary Biosocial Perspective, 13(3), 327–344.Find this resource:
Maestripieri, D., Hoffman, C. L., Anderson, G. M., Carter, C. S., & Higley, J. D. (2009). Mother-infant interactions in free-ranging rhesus macaques: Relationships between physiological and behavioral variables. Physiology & Behavior, 96(4–5), 613–619.Find this resource:
Magiakou, M., Mastorakos, G., Rabin, D., Dubbert, B., Gold, P., & Chrousos, G. (1996). Hypothalamic corticotropin-releasing hormone suppression during the postpartum period: Implications for the increase in psychiatric manifestations at this time. Journal of Clinical Endocrinology and Metabolism, 81(5), 1912–1917.Find this resource:
Mah, B. L., Van Ijzendoorn, M. H., Out, D., Smith, R., & Bakermans-Kranenburg, M. J. (2017). The effects of intranasal oxytocin administration on sensitive caregiving in mothers with postnatal depression. Child Psychiatry & Human Development, 48(2), 308–315.Find this resource:
Mank, J. E., Promislow, D. E., & Avise, J. C. (2005). Phylogenetic perspectives in the evolution of parental care in ray-finned fishes. Evolution, 59(7), 1570–1578.Find this resource:
Mann, M., Michael, S. D., & Svare, B. (1980). Ergot drugs suppress plasma prolactin and lactation but not aggression in parturient mice. Hormones and Behavior, 14(4), 319–328.Find this resource:
Marrone, B. L., Rodriguez-Sierra, J. F., & Feder, H. H. (1977). Lordosis: Inhibiting effects of progesterone in the female rat. Hormones and Behavior, 8(3), 391–402.Find this resource:
Mas, F., & Kölliker, M. (2008). Maternal care and offspring begging in social insects: Chemical signalling, hormonal regulation and evolution. Animal Behaviour, 76, 1121–1131.Find this resource:
Mathur, R. S., Landgrebe, S., & Williamson, H. O. (1980). Progesterone, 17-hydroxyprogesterone, estradiol, and estriol in late pregnancy and labor. American Journal of Obstetrics and Gynecology, 136(1), 25–27.Find this resource:
McCarthy, M. M. (1990). Oxytocin inhibits infanticide in female house mice (Mus domesticus). Hormones and Behavior, 24(3), 365–375.Find this resource:
McCarthy, M. M., Curran, G. H., & Siegel, H. I. (1994). Evidence for the involvement of prolactin in the maternal behavior of the hamster. Physiology & Behavior, 55(1), 181–184.Find this resource:
McCormack, J. T., & Greenwald, G. S. (1974). Progesterone and oestradiol-17beta concentrations in the peripheral plasma during pregnancy in the mouse. The Journal of Endocrinology, 62(1), 101–107.Find this resource:
McGarrigle, H. H., & Lachelin, G. C. (1984). Increasing saliva (free) oestriol to progesterone ratio in late pregnancy: A role for oestriol in initiating spontaneous labour in man? British medical Journal (Clinical Research ed.), 289(6443), 457–459.Find this resource:
McKenna, N. J. (2015). Gonadal steroid action. Knobil and Neill’s Physiology of Reproduction, 313–333.Find this resource:
McNeilly, A. S. (2001). Neuroendocrine changes and fertility in breast-feeding women. Progress in Brain Research, 133, 207–214.Find this resource:
Meddle, S. L., Bishop, V. R., Gkoumassi, E., van Leeuwen, F. W., & Douglas, A. J. (2007). Dynamic changes in oxytocin receptor expression and activation at parturition in the rat brain. Endocrinology, 148(10), 5095–5104.Find this resource:
Mehta, D., Eapen, V., Kohlhoff, J., Mendoza Diaz, A., Barnett, B., Silove, D., & Dadds, M. R. (2016). Genetic regulation of maternal oxytocin response and its influences on maternal behavior. Neural Plasticity, 2016, 5740365.Find this resource:
Merchenthaler, I., Lane, M. V., Numan, S., & Dellovade, T. L. (2004). Distribution of estrogen receptor α and β in the mouse central nervous system: In vivo autoradiographic and immunocytochemical analyses. Journal of Comparative Neurology, 473(2), 270–291.Find this resource:
Meurisse, M., Gonzalez, A., Delsol, G., Caba, M., Levy, F., & Poindron, P. (2005). Estradiol receptor-α expression in hypothalamic and limbic regions of ewes is influenced by physiological state and maternal experience. Hormones and Behavior, 48(1), 34–43.Find this resource:
Miller, S. M., & Lonstein, J. S. (2005). Dopamine d1 and d2 receptor antagonism in the preoptic area produces different effects on maternal behavior in lactating rats. Behavioral Neuroscience, 119(4), 1072–1083.Find this resource:
Miller, S. M., & Lonstein, J. S. (2009). Dopaminergic projections to the medial preoptic area of postpartum rats. Neuroscience, 159(4), 1384–1396.Find this resource:
Moltz, H., Lubin, M., Leon, M., & Numan, M. (1970). Hormonal induction of maternal behavior in the ovariectomized nulliparous rat. Physiology & Behavior, 5(12), 1373–1377.Find this resource:
Morrell, J. I., Schwanzel-Fukuda, M., Fahrbach, S. E., & Pfaff, D. W. (1984). Axonal projections and peptide content of steroid hormone concentrating neurons. Peptides, 5(Suppl 1), 227–239.Find this resource:
Moura, D., Canavarro, M. C., & Figueiredo-Braga, M. (2016). Oxytocin and depression in the perinatal period—a systematic review. Archives of Women’s Mental Health, 19(4), 561–570.Find this resource:
Mulac-Jericevic, B., Lydon, J. P., DeMayo, F. J., & Conneely, O. M. (2003). Defective mammary gland morphogenesis in mice lacking the progesterone receptor B isoform. Proceedings of the National Academy of Sciences, 100(17), 9744–9749.Find this resource:
Murakami, G. (2016). Distinct effects of estrogen on mouse maternal behavior: The contribution of estrogen synthesis in the brain. PloS One, 11(3), e0150728.Find this resource:
Nelson, W. O., & Pfiffner, J. J. (1930). An experimental study of the factors concerned in mammary growth and in milk secretion. Proceedings of the Society for Experimental Biology and Medicine, 28(1), 1–2.Find this resource:
Nephew, B. C., & Bridges, R. S. (2008a). Arginine vasopressin V1a receptor antagonist impairs maternal memory in rats. Physiology & Behavior, 95(1–2), 182–186.Find this resource:
Nephew, B. C., & Bridges, R. S. (2008b). Central actions of arginine vasopressin and a V1a receptor antagonist on maternal aggression, maternal behavior, and grooming in lactating rats. Pharmacology Biochemistry and Behavior, 91(1), 77–83.Find this resource:
Nephew, B. C., Byrnes, E. M., & Bridges, R. S. (2010). Vasopressin mediates enhanced offspring protection in multiparous rats. Neuropharmacology, 58(1), 102–106.Find this resource:
Neumann, I. D., Maloumby, R., Beiderbeck, D. I., Lukas, M., & Landgraf, R. (2013). Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice. Psychoneuroendocrinology, 38(10), 1985–1993.Find this resource:
Neumann, I. D., Wegener, G., Homberg, J. R., Cohen, H., Slattery, D. A., Zohar, J., . . . Mathe, A. A. (2011). Animal models of depression and anxiety: What do they tell us about human condition?Progress in Neuro-psychopharmacology and Biology Psychiatry, 35(6), 1357–1375.Find this resource:
Nishimori, K., Young, L. J., Guo, Q., Wang, Z., Insel, T. R., & Matzuk, M. M. (1996). Oxytocin is required for nursing but is not essential for parturition or reproductive behavior. Proceedings of the National Academy of Sciences of the United States of America, 93(21), 11699–11704.Find this resource:
Numan, M., & Smith, H. G. (1984). Maternal behavior in rats: Evidence for the involvement of preoptic projections to the ventral tegmental area. Behavioral Neuroscience, 98(4), 712–727.Find this resource:
Numan, M., Leon, M., & Moltz, H. (1972). Interference with prolactin release and the maternal behavior of female rats. Hormones and Behavior, 3(1), 29–38.Find this resource:
Numan, M., Roach, J. K., del Cerro, M. C., Guillamon, A., Segovia, S., Sheehan, T. P., & Numan, M. J. (1999). Expression of intracellular progesterone receptors in rat brain during different reproductive states, and involvement in maternal behavior. Brain Research, 830(2), 358–371.Find this resource:
Numan, M. (1978). Progesterone inhibition of maternal behavior in the rat. Hormones and Behavior, 11(2), 209–231.Find this resource:
Numan, M., & Stolzenberg, D. S. (2009). Medial preoptic area interactions with dopamine neural systems in the control of the onset and maintenance of maternal behavior in rats. Frontiers in Neuroendocrinology, 30(1), 46–64.Find this resource:
Numan, M., Rosenblatt, J. S., & Komisaruk, B. R. (1977). Medial preoptic area and onset of maternal behavior in the rat. Journal of Comparative and Physiological Psychology, 91(1), 146.Find this resource:
Numan, M., Stolzenberg, D. S, Dellevigne, A. A., Correnti, C. M., & Numan, M. J. (2009). Temporary inactivation of ventral tegmental area neurons with either muscimol or baclofen reversibly disrupts maternal behavior in rats through different underlying mechanisms. Behavioral Neuroscience, 123(4), 740–751.Find this resource:
Numan, M., Numan, M. J., Pliakou, N., Stolzenberg, D. S., Mullins, O. J., Murphy, J. M., & Smith, C. D. (2005). The effects of D1 or D2 dopamine receptor antagonism in the medial preoptic area, ventral pallidum, or nucleus accumbens on the maternal retrieval response and other aspects of maternal behavior in rats. Behavioral Neuroscience, 119(6), 1588–1604.Find this resource:
Oakey, R. E. (1975). Serum cortisol binding capacity and cortisol concentration in the pregnant baboon and its fetus during gestation. Endocrinology, 97(4), 1024–1029.Find this resource:
Oettl, L.-L., Ravi, N., Schneider, M., Scheller, M. F., Schneider, P., Mitre, M., . . . Young, W. S. (2016). Oxytocin enhances social recognition by modulating cortical control of early olfactory processing. Neuron, 90(3), 609–621.Find this resource:
Ogawa, S., Taylor, J. A., Lubahn, D. B., Korach, K. S., & Pfaff, D. W. (1996). Reversal of sex roles in genetic female mice by disruption of estrogen receptor gene. Neuroendocrinology, 64(6), 467–470.Find this resource:
Ogawa, S., Eng, V., Taylor, J., Lubahn, D. B., Korach, K. S., & Pfaff, D. W. (1998). Roles of estrogen receptor-α gene expression in reproduction-related behaviors in female mice. Endocrinology, 139(12), 5070–5081.Find this resource:
Olazabal, D. E., & Young, L. J. (2006a). Species and individual differences in juvenile female alloparental care are associated with oxytocin receptor density in the striatum and the lateral septum. Hormones and Behavior, 49(5), 681–687.Find this resource:
Olazabal, D. E., & Young, L. J. (2006b). Oxytocin receptors in the nucleus accumbens facilitate ‘spontaneous’ maternal behavior in adult female prairie voles. Neuroscience, 141(2), 559–568.Find this resource:
Olazabal, D. E., & Alsina-Llanes, M. (2016). Are age and sex differences in brain oxytocin receptors related to maternal and infanticidal behavior in naive mice? Hormones and Behavior, 77, 132–140.Find this resource:
Österlund, M. K., Gustafsson, J.-Å., Keller, E., & Hurd, Y. L. (2000). Estrogen receptor β (ERβ) messenger ribonucleic acid (mRNA) expression within the human forebrain: Distinct distribution pattern to ERα mRNA. The Journal of Clinical Endocrinology & Metabolism, 85(10), 3840–3846.Find this resource:
Owens, P. C., Smith, R., Brinsmead, M. W., Hall, C., Rowley, M., Hurt, D., . . . Lewin, T. (1987). Postnatal disappearance of the pregnancy-associated reduced sensitivity of plasma cortisol to feedback inhibition. Life Sciences, 41(14), 1745–1750.Find this resource:
Pagani, J. H., Williams Avram, S. K., Cui, Z., Song, J., Mezey, E., Senerth, J. M., . . . Young, W. S. (2015). Raphe serotonin neuron-specific oxytocin receptor knockout reduces aggression without affecting anxiety-like behavior in male mice only. Genes, Brain and Behavior, 14(2), 167–176.Find this resource:
Parry, B. L., Sorenson, D. L., Meliska, C. J., Basavaraj, N., Zirpoli, G. G., Gamst, A., & Hauger, R. (2003). Hormonal basis of mood and postpartum disorders. Current Women’s Health Reports, 3(3), 230–235.Find this resource:
Pedersen, C. A., & Prange, A. J., Jr. (1979). Induction of maternal behavior in virgin rats after intracerebroventricular administration of oxytocin. Proceedings of the National Academy of Sciences of the United States of America, 76(12), 6661–6665.Find this resource:
Pedersen, C. A., & Boccia, M. L. (2003). Oxytocin antagonism alters rat dams’ oral grooming and upright posturing over pups. Physiology & Behavior, 80 (2–3), 233–241.Find this resource:
Pedersen, C. A., Ascher, J. A., Monroe, Y. L., & Prange, A. J., Jr. (1982). Oxytocin induces maternal behavior in virgin female rats. Science, 216(4546), 648–650.Find this resource:
Pedersen, C. A., Caldwell, J. D., McGuire, M., & Evans, D. L. (1991). Corticotropin-releasing hormone inhibits maternal behavior and induces pup-killing. Life Sci, 48(16), 1537–1546.Find this resource:
Pedersen, C. A., Vadlamudi, S. V., Boccia, M. L., & Amico, J. A. (2006). Maternal behavior deficits in nulliparous oxytocin knockout mice. Genes, Brain and Behavior, 5(3), 274–281.Find this resource:
Pedersen, C. A., Caldwell, J. D., Johnson, M. F., Fort, S. A., & Prange, A. J., Jr. (1985). Oxytocin antiserum delays onset of ovarian steroid-induced maternal behavior. Neuropeptides, 6(2), 175–182.Find this resource:
Pedersen, C. A., Caldwell, J. D., Walker, C., Ayers, G., & Mason, G. A. (1994). Oxytocin activates the postpartum onset of rat maternal behavior in the ventral tegmental and medial preoptic areas. Behavioral Neuroscience, 108(6), 1163–1171.Find this resource:
Pepe, G., & Rothchild, I. (1972). The effect of hypophysectomy on day 12 of pregnancy on the serum progesterone level and time of parturition in the rat. Endocrinology, 91(5), 1380–1385.Find this resource:
Perrin, G., Meurisse, M., & Lévy, F. (2007). Inactivation of the medial preoptic area or the bed nucleus of the stria terminalis differentially disrupts maternal behavior in sheep. Hormones and Behavior, 52(4), 461–473.Find this resource:
Pi, X. J., & Grattan, D. R. (1999). Increased expression of both short and long forms of prolactin receptor mRNA in hypothalamic nuclei of lactating rats. Journal of Molecular Endocrinology, 23(1), 13–22.Find this resource:
Poindron, P., & Le Neindre, P. (1980). Endocrine and sensory regulation of maternal behavior in the ewe. Advances in the Study of Behavior, 11, 75–119.Find this resource:
Prevost, M., Zelkowitz, P., Tulandi, T., Hayton, B., Feeley, N., Carter, C. S., . . . Abenhaim, H. (2014). Oxytocin in pregnancy and the postpartum: Relations to labor and its management. Frontiers in Public Health, 2, 1.Find this resource:
Price, A. K., & Bridges, R. S. (2014). The effects of bromocriptine treatment during early pregnancy on postpartum maternal behaviors in rats. Developmental Psychobiology, 56(6), 1431–1437.Find this resource:
Pryce, C. R., Dobeli, M., & Martin, R. D. (1993). Effects of sex steroids on maternal motivation in the common marmoset (Callithrix jacchus): Development and application of an operant system with maternal reinforcement. Journal of Comparative Psychology, 107(1), 99–115.Find this resource:
Pryce, C. R., Abbott, D. H., Hodges, J. K., & Martin, R. D. (1988). Maternal behavior is related to prepartum urinary estradiol levels in red-bellied tamarin monkeys. Physiology & Behavior, 44(6), 717–726.Find this resource:
Ramirez, S. M., Bardi, M., French, J. A., & Brent, L. (2004). Hormonal correlates of changes in interest in unrelated infants across the peripartum period in female baboons (Papio hamadryas anubis sp.). Hormones and Behavior, 46(5), 520–528.Find this resource:
Rees, S. L., Panesar, S., Steiner, M., & Fleming, A. S. (2004). The effects of adrenalectomy and corticosterone replacement on maternal behavior in the postpartum rat. Hormones and Behavior, 46(4), 411–419.Find this resource:
Rees, S. L., Panesar, S., Steiner, M., & Fleming, A. S. (2006). The effects of adrenalectomy and corticosterone replacement on induction of maternal behavior in the virgin female rat. Hormones and Behavior, 49(3), 337–345.Find this resource:
Reyes, F. I., Winter, J. S., Faiman, C., & Hobson, W. C. (1975). Serial serum levels of gonadotropins, prolactin and sex steroids in the nonpregnant and pregnant chimpanzee. Endocrinology, 96(6), 1447–1455.Find this resource:
Ribeiro, A. C., Musatov, S., Shteyler, A., Simanduyev, S., Arrieta-Cruz, I., Ogawa, S., & Pfaff, D. W. (2012). siRNA silencing of estrogen receptor-α expression specifically in medial preoptic area neurons abolishes maternal care in female mice. Proceedings of the National Academy of Sciences, 109(40), 16324–16329.Find this resource:
Rich, M. E., deCardenas, E. J., Lee, H. J., & Caldwell, H. K. (2014). Impairments in the initiation of maternal behavior in oxytocin receptor knockout mice. PLoS One, 9(6), e98839.Find this resource:
Riddle, O., Bates, R. W., & Dykshorn, S. W. (1933). The preparation, identification and assay of prolactin—a hormone of the anterior pituitary. American Journal of Physiology-Legacy Content, 105(1), 191–216.Find this resource:
Riddle, O., Lahr, E. L., & Bates, R. W. (1935). Maternal behavior induced in virgin rats by prolactin. Proceedings of the Society for Experimental Biology and Medicine, 32(5), 730–734.Find this resource:
Riddle, O., Lahr, E. L., & Bates, R. W. (1942). The role of hormones in the initiation of maternal behavior in rats. American Journal of Physiology-Legacy Content, 137(2), 299–317.Find this resource:
Rivas, M., Torterolo, P., Ferreira, A., & Benedetto, L. (2016). Hypocretinergic system in the medial preoptic area promotes maternal behavior in lactating rats. Peptides, 81, 9–14.Find this resource:
Roberts, R. L., Jenkins, K. T., Lawler, T., Jr., Wegner, F. H., & Newman, J. D. (2001). Bromocriptine administration lowers serum prolactin and disrupts parental responsiveness in common marmosets (Callithrix j. jacchus). Hormones and Behavior, 39(2), 106–112.Find this resource:
Rocha, J. B. T., Soares, F. A. A., & De Mello, C. F. (2002). Influence of the test situation on pup retrieval behavior of normal and undernourished lactating rats. Brazilian Journal of Medical and Biological Research, 35(1), 91–97.Find this resource:
Rodriguez-Sierra, J. F., & Rosenblati, J. S. (1977). Does prolactin play a role in estrogen-induced maternal behavior in rats: Apomorphine reduction of prolactin release. Hormones and Behavior, 9(1), 1–7.Find this resource:
Rondini, T. A., Donato, J., Jr., Rodrigues Bde, C., Bittencourt, J. C., & Elias, C. F. (2010). Chemical identity and connections of medial preoptic area neurons expressing melanin-concentrating hormone during lactation. Journal of Chemical Neuroanatomy, 39(1), 51–62.Find this resource:
Rosenblatt, J. S. (1969). The development of maternal responsiveness in the rat. American Journal of Orthopsychiatry, 39(1), 36–56.Find this resource:
Rosenblatt, J. S., & Siegel, H. I. (1981a). Factors governing the onset and maintenance of maternal behavior among nonprimate mammals. In David J. Gubernick (Ed.), Parental care in mammals (pp. 13–76). Boston, MA: Springer.Find this resource:
Rosenblatt, J. S., & Siegel, H. I. (1981b). Factors governing the onset and maintenance of maternal behavior among nonprimate mammals. In Parental care in mammals (pp. 13–76). Boston, MA: Springer.Find this resource:
Rowell, T. E. (1960). On the retrieving of young and other behaviour in lactating golden hamsters. Journal of Zoology, 135(2), 265–282.Find this resource:
Rubin, B. S., Menniti, F. S., & Bridges, R. S. (1983). Intracerebroventricular administration of oxytocin and maternal behavior in rats after prolonged and acute steroid pretreatment. Hormones and Behavior, 17(1), 45–53.Find this resource:
Saltzman, W., & Abbott, D. H. (2005). Diminished maternal responsiveness during pregnancy in multiparous female common marmosets. Hormones and Behavior, 47(2), 151–163.Find this resource:
Saltzman, W., & Abbott, D. H. (2009). Effects of elevated circulating cortisol concentrations on maternal behavior in common marmoset monkeys (Callithrix jacchus). Psychoneuroendocrinology, 34(8), 1222–1234.Find this resource:
Saltzman, W., Boettcher, C. A., Post, J. L., & Abbott, D. H. (2011). Inhibition of maternal behaviour by central infusion of corticotrophin-releasing hormone in marmoset monkeys. Journal of Neuroendocrinology, 23(11), 1139–1148.Find this resource:
Saltzman, W., & Maestripieri, D. (2011). The neuroendocrinology of primate maternal behavior. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 35(5), 1192–1204.Find this resource:
Sanchez-Andrade, G., & Kendrick, K. M. (2011). Roles of α-and β-estrogen receptors in mouse social recognition memory: Effects of gender and the estrous cycle. Hormones and Behavior, 59(1), 114–122.Find this resource:
Sanchez-Andrade, G., & Kendrick, K. M. (2009). The main olfactory system and social learning in mammals. Behavioural Brain Research, 200(2), 323–335.Find this resource:
Schreier, H. M. C., Bosquet Enlow, M., Ritz, T., Coull, B. A., Gennings, C., Wright, R. O., & Wright, R. J. (2016). Lifetime exposure to traumatic and other stressful life events and hair cortisol in a multi-racial/ethnic sample of pregnant women. Stress, 19(1), 45–52.Find this resource:
Seaton, B. (1978). Patterns of oestrogen and testosterone excretion during pregnancy in a gorilla (gorilla gorilla). Journal of Reproduction and Fertility, 53(2), 231–236.Find this resource:
Shamay-Tsoory, S. G., & Abu-Akel, A. (2016). The social salience hypothesis of oxytocin. Biological Psychiatry, 79(3), 194–202.Find this resource:
Sheehan, T., & Numan, M. (2002). Estrogen, progesterone, and pregnancy termination alter neural activity in brain regions that control maternal behavior in rats. Neuroendocrinology, 75(1), 12–23.Find this resource:
Sherin, J. E., Elmquist, J. K., Torrealba, F., & Saper, C. B. (1998). Innervation of histaminergic tuberomammillary neurons by GABAergic and galaninergic neurons in the ventrolateral preoptic nucleus of the rat. The Journal of Neuroscience, 18(12), 4705–4721.Find this resource:
Shimizu, K., Douke, C., Fujita, S., Matsuzawa, T., Tomonaga, M., Tanaka, M., . . . Hayashi, M. (2003). Urinary steroids, FSH and CG measurements for monitoring the ovarian cycle and pregnancy in the chimpanzee. Journal of Medical Primatology, 32(1), 15–22.Find this resource:
Shin, H., Park, Y. J., Ryu, H., & Seomun, G. A. (2008). Maternal sensitivity: A concept analysis. Journal of Advanced Nursing, 64(3), 304–314.Find this resource:
Shingo, T., Gregg, C., Enwere, E., Fujikawa, H., Hassam, R., Geary, C., . . . Weiss, S. (2003). Pregnancy-stimulated neurogenesis in the adult female forebrain mediated by prolactin. Science, 299(5603), 117–120.Find this resource:
Shughrue, P. J., Lane, M. V., & Merchenthaler, I. (1997). Comparative distribution of estrogen receptor‐α and‐β mRNA in the rat central nervous system. Journal of Comparative Neurology, 388(4), 507–525.Find this resource:
Siegel, H. I., & Rosenblatt, J. S. (1978). Effects of adrenalectomy on maternal behavior in pregnancy-terminated rats. Physiology & Behavior, 21(5), 831–833.Find this resource:
Silber, M., Larsson, B., & Uvnäs-Moberg, K. (1991). Oxytocin, somatostatin, insulin and gastrin concentrations vis‐à‐vis late pregnancy, breastfeeding and oral contraceptives. Acta obstetricia et gynecologica Scandinavica, 70(4–5), 283–289.Find this resource:
Simerly, R. B., Swanson, L. W., Chang, C., & Muramatsu, M. (1990). Distribution of androgen and estrogen receptor mRNA‐containing cells in the rat brain: An in situ hybridization study. Journal of Comparative Neurology, 294(1), 76–95.Find this resource:
Skofitsch, G., & Jacobowitz, D. M. (1986). Quantitative distribution of galanin-like immunoreactivity in the rat central nervous system. Peptides, 7(4), 609–613.Find this resource:
Skrundz, M., Bolten, M., Nast, I., Hellhammer, D. H., & Meinlschmidt, G. (2011). Plasma oxytocin concentration during pregnancy is associated with development of postpartum depression. Neuropsychopharmacology, 36(9), 1886–1893.Find this resource:
Slattery, D. A., & Neumann, I. D. (2008). No stress please! Mechanisms of stress hyporesponsiveness of the maternal brain. The Journal of Physiology, 586(2), 377–385.Find this resource:
Slattery, D. A., & Hillerer, K. M. (2016). The maternal brain under stress: Consequences for adaptive peripartum plasticity and its potential functional implications. Frontiers in Neuroendocrinology, 41, 114–128.Find this resource:
Slotnick, B. M. (1967). Intercorrelations of maternal activities in the rat. Animal Behaviour, 15(2–3), 267–269.Find this resource:
Smith, M. S., & Neill, J. D. (1977). Inhibition of gonadotropin secretion during lactation in the rat: Relative contribution of suckling and ovarian steroids. Biology of Reproduction, 17(2), 255–261.Find this resource:
Smith, M. J., Perrett, D. I., Jones, B. C., Cornwell, R. E., Moore, F. R., Feinberg, D. R., . . . Hillier, S. G. (2006). Facial appearance is a cue to oestrogen levels in women. Proceedings of the Royal Society B: Biological Science, 273(1583), 135–140.Find this resource:
Smith, R., Wickings, E. J., Bowman, M. E., Belleoud, A., Dubreuil, G., Davies, J. J., & Madsen, G. (1999). Corticotropin-releasing hormone in chimpanzee and gorilla pregnancies. The Journal of Clinical Endocrinology and Metabolism, 84(8), 2820–2825.Find this resource:
Smith, R., Smith, J. I., Shen, X., Engel, P. J., Bowman, M. E., McGrath, S. A., . . . Smith, D. W. (2009). Patterns of plasma corticotropin-releasing hormone, progesterone, estradiol, and estriol change and the onset of human labor. The Journal of Clinical Endocrinology and Metabolism, 94(6), 2066–2074.Find this resource:
Sridaran, R., Basuray, R., & Gibori, G. (1981). Source and regulation of testosterone secretion in pregnant and pseudopregnant rats. Endocrinology, 108(3), 855–861.Find this resource:
Stallings, J., Fleming, A.S., Corter, C., Worthman, C., & Steiner, M. (2001). The effects of infant cries and odors on sympathy, cortisol, and autonomic responses in new mothers and nonpostpartum women. Parenting, 1, 71–100.Find this resource:
Stanton, M. A., Heintz, M. R., Lonsdorf, E. V., Santymire, R. M., Lipende, I., & Murray, C. M. (2015). Maternal behavior and physiological stress levels in wild chimpanzees (Pan troglodytes schweinfurthii). International Journal of Primatology, 36(3), 473–488.Find this resource:
Steele, M., Moltz, H., & Rowland, D. (1976). Adrenal disruption of maternal behavior in the Caesarean-sectioned rat. Hormones and Behavior, 7(4), 473–479.Find this resource:
Steinetz, B. G., Randolph, C., & Mahoney, C. J. (1992). Serum concentrations of relaxin, chorionic gonadotropin, estradiol-17 beta, and progesterone during the reproductive cycle of the chimpanzee (Pan troglodytes). Endocrinology, 130(6), 3601–3607.Find this resource:
Stern, J. M., & Levine, S. (1972). Pituitary-adrenal activity in the postpartum rat in the absence of suckling stimulation. Hormones and Behavior, 3(3), 237–246.Find this resource:
Stern, J. M., & Johnson, S. K. (1989). Perioral somatosensory determinants of nursing behavior in Norway rats (Rattus norvegicus). Journal of Comparative Psychology, 103(3), 269.Find this resource:
Stolzenberg, D. S., & Rissman, E. F. (2011). Oestrogen‐independent, experience‐induced maternal behaviour in female mice. Journal of Neuroendocrinology, 23(4), 345–354.Find this resource:
Stolzenberg, D. S., & Champagne, F. A. (2016). Hormonal and non-hormonal bases of maternal behavior: The role of experience and epigenetic mechanisms. Hormones and Behavior, 77, 204–210.Find this resource:
Stolzenberg, D. S., Zhang, K. Y., Luskin, K., Ranker, L., Balkema, J., Bress, J., & Numan, M. (2009). A single injection of 17β-estradiol at the time of pup presentation promotes the onset of maternal behavior in pregnancy-terminated rats. Hormones and Behavior, 56(1), 121–127.Find this resource:
Storey, A. E., & Ziegler, T. E. (2016). Primate paternal care: Interactions between biology and social experience. Hormones and Behavior, 77, 260–271.Find this resource:
Strathearn, L. (2011). Maternal neglect: Oxytocin, dopamine and the neurobiology of attachment. Journal of Neuroendocrinology, 23(11), 1054–1065.Find this resource:
Strathearn, L., Fonagy, P., Amico, J., & Montague, P. R. (2009). Adult attachment predicts maternal brain and oxytocin response to infant cues. Neuropsychopharmacology: Official publication of the American College of Neuropsychopharmacology, 34 (13), 2655–2666.Find this resource:
Strathearn, L., Iyengar, U., Fonagy, P., & Kim, S. (2012). Maternal oxytocin response during mother–infant interaction: Associations with adult temperament. Hormones and Behavior, 61(3), 429–435.Find this resource:
Stricker, P. (1928). Action of the anterior lobe of the pituitary gland on the milky rise. Compendiums Rendus Society of Biology, 99, 1978–1980.Find this resource:
Stuebe, A. M., Grewen, K., & Meltzer-Brody, S. (2013). Association between maternal mood and oxytocin response to breastfeeding. Journal of Women’s Health, 22(4), 352–361.Find this resource:
Sweatt, J. D. (2009). Experience-dependent epigenetic modifications in the central nervous system. Biological Psychiatry, 65(3), 191–197.Find this resource:
Takayanagi, Y., Yoshida, M., Bielsky, I. F., Ross, H. E., Kawamata, M., Onaka, T., . . . Nishimori, K. (2005). Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice. Proceedings of the National Academy of Sciences of the United States of America, 102(44), 16096–16101.Find this resource:
Talge, N. M., Talge, N. M., Neal, C., Glover, V., the Early Stress, Translational Research, Prevention Science Network, Fetal, Neonatal Experience on, Child, & Adolescent Mental, Health. (2007). Antenatal maternal stress and long-term effects on child neurodevelopment: How and why? Journal of Child Psychology and Psychiatry, 48 (3–4), 245–261.Find this resource:
Talge, N. M., Holzman, C., Wang, J., Lucia, V., Gardiner, J., & Breslau, N. (2010). Late-preterm birth and its association with cognitive and socioemotional outcomes at 6 years of age. Pediatrics, 126(6), 1124–1131.Find this resource:
Taya, K., & Greenwald, G. S. (1982). Peripheral blood and ovarian levels of sex steroids in the lactating rat. Endocrinologia Japonica, 29(4), 453–459.Find this resource:
Taylor, A., Glover, V., Marks, M., & Kammerer, M. (2009). Diurnal pattern of cortisol output in postnatal depression. Psychoneuroendocrinology, 34(8), 1184–1188.Find this resource:
Taylor, S. E., Saphire-Bernstein, S., & Seeman, T. E. (2010). Are plasma oxytocin in women and plasma vasopressin in men biomarkers of distressed pair-bond relationships? Psychological Science, 21(1), 3–7.Find this resource:
Terkel, J., & Rosenblatt, J. S. (1972). Humoral factors underlying maternal behavior at parturition: Cross transfusion between freely moving rats. Journal of Comparative and Physiological Psychology, 80(3), 365.Find this resource:
Tharner, A., Luijk, M. P., Raat, H., Ijzendoorn, M. H., Bakermans-Kranenburg, M. J., Moll, H. A., . . . Tiemeier, H. (2012). Breastfeeding and its relation to maternal sensitivity and infant attachment. Journal of Developmental and Behavioral Pediatrics, 33(5), 396–404.Find this resource:
Thoman, E. B., & Levine, S. (1970). “Effects of adrenalectomy on maternal behavior in rats.” Developmental Psychobiology, 3(4), 237–244.Find this resource:
Tobiansky, D. J., Will, R. G., Lominac, K. D., Turner, J. M., Hattori, T., Krishnan, K., . . . Dominguez, J. M. (2016). Estradiol in the preoptic area regulates the dopaminergic response to cocaine in the nucleus accumbens. Neuropsychopharmacology, 41(7), 1897.Find this resource:
Torner, L., Toschi, N., Nava, G., Clapp, C., & Neumann, I. D. (2002). Increased hypothalamic expression of prolactin in lactation: Involvement in behavioural and neuroendocrine stress responses. European Journal of Neuroscience, 15(8), 1381–1389.Find this resource:
Trumbo, S. T. (2002). Hormonal regulation of parental care in insects. In D. W. Pfaff, et al. (Eds.), Hormones, brain and behavior (pp. 115–139). New York, NY: Academic Press.Find this resource:
Tsujino, N., & Sakurai, T. (2013). Role of orexin in modulating arousal, feeding, and motivation. Front Behavioral Neuroscience, 7, 28.Find this resource:
Tsuneoka, Y., Maruyama, T., Yoshida, S., Nishimori, K., Kato, T., Numan, M., & Kuroda, K. O. (2013). Functional, anatomical, and neurochemical differentiation of medial preoptic area subregions in relation to maternal behavior in the mouse. Journal of Comparative Neurology, 521(7), 1633–1663.Find this resource:
Tu, M. T., Lupien, S. J., & Walker, C.-D. (2006). Diurnal salivary cortisol levels in postpartum mothers as a function of infant feeding choice and parity. Psychoneuroendocrinology, 31(7), 812–824.Find this resource:
Tulchinsky, D., Hobel, C. J., Yeager, E., & Marshall, J. R. (1972). Plasma estrone, estradiol, estriol, progesterone, and 17-hydroxyprogesterone in human pregnancy. I. Normal pregnancy. American Journal of Obstetrics and Gynecology, 112(8), 1095–1100.Find this resource:
Tulchinsky, D., Frigoletto, F. D., Jr., Ryan, K. J., & Fishman, J. (1975). Plasma estetrol as an index of fetal well-being. The Journal of Clinical Endocrinology and Metabolism, 40(4), 560–567.Find this resource:
Tulchinsky, D., & Hobel, C. J. (1973). Plasma human chorionic gonadotropin, estrone, estradiol, estriol, progesterone, and 17α-hydroxyprogesterone in human pregnancy: III. Early normal pregnancy. American Journal of Obstetrics and Gynecology, 117(7), 884–893.Find this resource:
Turner, R. A., Altemus, M., Yip, D. N., Kupferman, E., Fletcher, D., Bostrom, A., . . . & Amico, J. A. (2002). Effects of emotion on oxytocin, prolactin, and ACTH in women. Stress, 5(4), 269–276.Find this resource:
Uvnäs‐Moberg, K., Widström, A.‐M., Werner, S., Matthiesen, A.‐S., & Winberg, J. (1990). Oxytocin and prolactin levels in breast‐feeding women. Correlation with milk yield and duration of breast‐feeding. Acta obstetricia et gynecologica Scandinavica, 69(4), 301–306.Find this resource:
Van der Post, J. A. M., et al. (1997). Vasopressin and oxytocin levels during normal pregnancy: Effects of chronic dietary sodium restriction. Journal of Endocrinology, 152(3), 345–354.Find this resource:
van Leengoed, E., Kerker, E., & Swanson, H. H. (1987). Inhibition of post-partum maternal behaviour in the rat by injecting an oxytocin antagonist into the cerebral ventricles. The Journal of Endocrinology, 112(2), 275–282.Find this resource:
Van Tol, H. H. M., Bolwerk, E. L. M, Liu, B., & Burbach, J. P. H. (1988). Oxytocin and vasopressin gene expression in the hypothalamo-neurohypophyseal system of the rat during the estrous cycle, pregnancy, and lactation. Endocrinology, 122(3), 945–951.Find this resource:
Vastagh, C., & Liposits, Z. (2017). Impact of proestrus on gene expression in the medial preoptic area of mice. Frontiers in Cellular Neuroscience, 11, 183.Find this resource:
Veenema, A. H., & Neumann, I. D. (2008). Central vasopressin and oxytocin release: Regulation of complex social behaviours. Progress in Brain Research, 170, 261–276.Find this resource:
Vilela, F. C., & Giusti-Paiva, A. (2011). Glucocorticoids disrupt neuroendocrine and behavioral responses during lactation. Endocrinology, 152(12), 4838–4845.Find this resource:
Wagner, C. K., & Morrell, J. I. (1995). In situ analysis of estrogen receptor mRNA expression in the brain of female rats during pregnancy. Brain Research. Molecular Brain Research, 33(1), 127–135.Find this resource:
Walker, C.-D., Toufexis, D. J., & Burlet, A. (2001). Hypothalamic and limbic expression of CRF and vasopressin during lactation: Implications for the control of ACTH secretion and stress hyporesponsiveness. Progress in Brain Research, 133, 99–110.Find this resource:
Wamboldt, M. Z., & Insel, T. R. (1987). The ability of oxytocin to induce short latency maternal behavior is dependent on peripheral anosmia. Behavioral Neuroscience, 101(3), 439–441.Find this resource:
Wang, L. P., Geng, R. Q., Zhang, X. N., & Sun, W. (2015). Identification of SNPs within the PRLR gene and effects on maternal behavior in sheep. Genetics and Molecular Research, 14(4), 17536–17543.Find this resource:
Warren, W. B., Patrick, S. L., & Goland, R. S. (1992). Elevated maternal plasma corticotropin-releasing hormone levels in pregnancies complicated by preterm labor. American Journal of Obstetrics and Gynecology, 166(4), 1198–1207.Find this resource:
Wiesner, B. P., & Sheard, N. M. (1933). Maternal behavior in the rat.Find this resource:
Willcox, D. L., Yovich, J. L., McColm, S. C., & Phillips, J. M. (1985). Progesterone, cortisol and oestradiol-17 beta in the initiation of human parturition: Partitioning between free and bound hormone in plasma. British Journal of Obstetrics Gynaecology, 92(1), 65–71.Find this resource:
Windle, R. J., Brady, M. M., Kunanandam, T., Da Costa, A. P., Wilson, B. C., Harbuz, M., . . . Ingram, C. D. (1997). Reduced response of the hypothalamo-pituitary-adrenal axis to alpha1-agonist stimulation during lactation. Endocrinology, 138(9), 3741–3748.Find this resource:
Wise, D. A., & Pryor, T. L. (1977). Effects of ergocornine and prolactin on aggression in the postpartum golden hamster. Hormones and Behavior, 8(1), 30–39.Find this resource:
Workman, J. L., Gobinath, A. R., Kitay, N. F., Chow, C., Brummelte, S., & Galea, L. A. (2016). Parity modifies the effects of fluoxetine and corticosterone on behavior, stress reactivity, and hippocampal neurogenesis. Neuropharmacology, 105, 443–453.Find this resource:
Wu, S. C., & Zhang, Y. (2010). Active DNA demethylation: Many roads lead to Rome. Nature Reviews Molecular Cell Biology, 11(9), 607.Find this resource:
Wu, Z., Autry, A. E., Bergan, J. F., Watabe-Uchida, M., & Dulac, C. G. (2014). Galanin neurons in the medial preoptic area govern parental behavior. Nature, 509(7500), 325–330.Find this resource:
Yoshihara, C., Numan, M., & Kuroda, K. O. (2017). Oxytocin and parental behaviors. Current Topics in Behavioral Neurosciences, 35, 119–153.Find this resource:
Young, W. S., III, Shepard, E., Amico, J., Hennighausen, L., Wagner, K. U., LaMarca, M. E., . . . Ginns, E. I. (1996). Deficiency in mouse oxytocin prevents milk ejection, but not fertility or parturition. Journal of Neuroendocrinology, 8(11), 847–853.Find this resource:
Zarrow, M. X., Farooq, A., Denenberg, V. H., Sawin, P. B., & Ross, S. (1963). Maternal behaviour in the rabbit: Endocrine control of maternal nest building. Journal of Reproduction and Fertility, 6, 375–383.Find this resource:
Zarrow, M. X., Sawin, P. B., Ross, S., Denenberg, V. H., Crary, D., Wilson, E. D., & Farooq, A. (1961). Maternal behaviour in the rabbit: Evidence for an endocrine basis of maternal-nest building and additional data on maternal-nest building in the Dutch-belted race. Reproduction, 2(2), 152–162.Find this resource:
Zhao, C., Saul, M. C., Driessen, T., & Gammie, S. C. (2012). Gene expression changes in the septum: Possible implications for microRNAs in sculpting the maternal brain. PLoS One, 7(6), e38602.Find this resource:
Ziegler, T. E., Scheffler, G., & Snowdon, C. T. (1995). The relationship of cortisol levels to social environment and reproductive functioning in female cotton-top tamarins, Saguinus oedipus. Hormones and Behavior, 29(3), 407–424.Find this resource: