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date: 28 June 2022

The Role of Oxytocin and Vasopressin in the Neural Regulation of Social Behaviorfree

The Role of Oxytocin and Vasopressin in the Neural Regulation of Social Behaviorfree

  • Heather K. CaldwellHeather K. CaldwellDepartment of Biological Sciences, Kent State University

Summary

Within the central nervous system, the neuropeptides oxytocin and vasopressin are key regulators of social behavior. While their effects can be nuanced, data suggest that they can influence behavior at multiple levels, including an individual’s personality/temperament, their social interactions in smaller groups (or one-on-one interactions), and their behavior in larger groups. At a mechanistic level, oxytocin and vasopressin help to integrate complex information—including aspects of an animal’s external and internal state—in order to shape behavioral output. Oxytocin and vasopressin help to modulate behaviors that bring animals together (i.e., cooperative behaviors) as well as behaviors that keep animals apart (i.e., competitive behaviors), with the modulatory effects often being species-, sex-, and context-dependent. While there continues to be extensive study of the function of these nonapeptides within individual brain nuclei, over the last two decades behavioral neuroendocrinologists have also made great strides in exploring their roles within larger brain networks that help to regulate social behavior. Looking forward, work on oxytocin and vasopressin will continue to shed light on how the neural regulation of social behaviors are similar, and/or dissimilar, within and between species and sexes, as well as provide insights into the neural chemistry that underlies behavioral differences in neurotypical and neurodivergent individuals.

Subjects

  • Neuroendocrine and Autonomic Systems

Introduction

In order to survive, animals need to be flexible about displays of social behaviors. This flexibility is often sex-specific and extends across numerous biological time scales, including a lifetime, a season, a reproductive cycle, a day, or moment to moment. What some neuroscientists seek to discover is how this flexibility is supported by neural circuitry, which presumably must be flexible as well. It is here that the neuroendocrine system comes into play, as it sits at the interface of the nervous system and the endocrine system, shaping aspects of physiology, including brain neural circuitry, and behavior.

The term “behavior” encompasses all responses that are observable, but the term “social behavior,” which is the focus of this article, can be defined as interactions between individuals that are thought to benefit one or more of the individuals (Wilson, 1975). This definition is inclusive of many types of behaviors that, for the most part, are often placed in one of two broad categories: cooperative behaviors, which include courtship behaviors, parental behaviors, and other attachment behaviors; and competitive behaviors, which include aggressive behaviors, territorial behaviors, and agonistic behaviors. While these two categories are very useful in helping researchers organize information associated with behavioral interactions between only a few individuals, they fall short of capturing all of the complexity associated with social interactions. A recent review by Raulo and Dantzer (2018) proposes a continuum of social behavior, which moves from the individual to the group, beginning with personality and ending with group-level cooperation. The advantage of this type of approach is that it is more inclusive of the totality of social behavior. For instance, if an individual animal is “shy” versus “bold,” there are likely differences in aspects of its neuroendocrine system that permeate numerous aspects of its social interactions (see reviews by Carere et al., 2010; French et al., 2018; Hau & Goymann, 2015; Johnson & Young, 2017; Koolhaas et al., 2010).

It is also important to recognize that social behaviors are central to many aspects of an animal’s life. It is through critical interactions with conspecifics that animals are able to meet many of their fundamental needs (i.e., sex, food, and shelter). It is also important to acknowledge that not all social behaviors are obviously “social.” For instance, feeding behaviors, which are often considered nonsocial behaviors, have a large social component in the context of group living (Samuni et al., 2018; Taylor et al., 2017; Ziegler & Crockford, 2017). The importance of the social context/environment is a theme that comes up repeatedly with respect to social behaviors, as it is the context that an animal finds itself in, along with its personal experience, that helps determine its behavioral response. As has been alluded to, there is great interest in understanding how an individual’s behavioral output is shaped at a neurochemical level. It is here that the neuroendocrine system comes in, playing a critical role in the regulation of social behavior.

The neuroendocrine system, if it is working properly, allows an animal to have adaptive changes in physiology and behavior. While there are numerous components of the neuroendocrine system, many of which directly contribute to the neural regulation of social behavior, such as the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-gonadal axis (Parhar et al., 2016; Raulo & Dantzer, 2018), this article focuses on the oxytocin and vasopressin systems. Due in part to the beautiful complexity of their social behavior as well as their oxytocin and vasopressin systems, mammals will be highlighted. However, for more information, there are reviews that include data on nonmammalian species, as well as those that explore how social behavior may be studied across taxa (Godwin & Thompson, 2012; Goodson & Kingsbury, 2013; O’Connell & Hofmann, 2011a; Prior & Soma, 2015; Robinson et al., 2019).

A Brief Overview of the Neuroendocrine System

At the heart of the neuroendocrine system is the hypothalamus, which is made up of many nuclei that collectively help support reproduction and maintain homeostasis (Griffin & Ojeda, 1988). It is here that sensory and autonomic nervous system information about an animal’s internal and external state, as well as an individual’s genotype and phenotype, are integrated. However, it is the output of the hypothalamus to the anterior and posterior pituitary, as well as numerous brain nuclei, that results in coordinated shifts in physiology and behavior. The next sections focus on the hypothalamic-neurohypophysial system and how the neurohormones of this system, oxytocin and vasopressin, act in the brain to affect social behaviors.

The Hypothalamic-Neurohypophysial System

The hypothalamic-neurohypophysial system is comprised predominantly of magnocellular neurosecretory cells whose cell bodies are found in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus. The axons of these neurosecretory cells extend through the median eminence and terminate on the capillaries of the posterior pituitary gland. Here they release oxytocin and vasopressin into the circulatory system and exert their effects on the periphery, which includes milk ejection (oxytocin) and salt and water balance (vasopressin). While the peripheral system can interact with other neuroendocrine axes, the stress axis in particular, there are also central projections of oxytocin and vasopressin that are critical to the modulation of social behaviors (for review, see Adkins-Regan, 2009; Bosch & Young, 2018; Caldwell, 2012; Caldwell & Albers, 2016; Caldwell et al., 2008; de Vries et al., 2012; Dumais & Veenema, 2016; Freeman & Bales, 2018; Johnson & Young, 2017; Lee et al., 2009). Centrally, oxytocin and vasopressin do not fall cleanly into the category of traditional neurotransmitters, because their effects are not always restricted to the postsynaptic cell, or the category of neurohormones, since they are not released into the bloodstream (Engelmann et al., 2000; Landgraf & Neumann, 2004; Leng & Ludwig, 2008). Rather, they appear to serve as neuromodulators.

Oxytocin and Vasopressin: Beyond the Hypothalamic-Neurohypophysial System

Oxytocin and vasopressin are evolutionarily ancient neuropeptides that are the result of a gene duplication approximately 500 million years ago (Gimpl & Fahrenholz, 2001). While both are highly conserved in their sequences among mammals, work in New World monkeys suggests that the structure of oxytocin has diverged from that of the other mammalian forms (Lee et al., 2011; Wallis, 2012). This divergence is thought to have occurred approximately 90 million years ago and has resulted in no less than six distinct forms of oxytocin (see the review by Mustoe et al., 2018). So far, the sequence changes have been found to affect intracellular signaling (Taylor et al., 2018), the structure of oxytocin and vasopressin receptors (Ren, Chin et al., 2014; Ren, Lu et al., 2015), and social behavior (for details, see French et al., 2018).

While oxytocin’s and vasopressin’s peripheral effects are quite profound, so, too, are their effects in the brain. Central oxytocin and vasopressin projections are widely distributed, with fibers found from the olfactory bulbs to the spinal cord (reviewed in Caldwell & Albers, 2016; Jurek & Neumann, 2018; Kelly & Goodson, 2014). These fibers come from two sources: smaller, parvocellular neurons located in the PVN and elsewhere (Castel & Morris, 1988; Ludwig & Leng, 2006), and magnocellular neurons of the SON and PVN, as well as accessory nuclei (Rhodes et al., 1981), that release oxytocin and vasopressin from nonsynaptic regions, such as dendrites, to produce important local effects (i.e., volume transmission; reviewed in Ludwig et al., 2016). This latter type of transmission, which results in a much more diffuse signal, can potentially impact a large number of neurons at multiple sites, likely up to 4–5 mm from their release site (Landgraf & Neumann, 2004; Ludwig et al., 2016). With respect to the neural regulation of social behavior, oxytocin and vasopressin projections to subcortical regions that are a part of the proposed vertebrate social behavioral neural network (SBNN), as well as to brain areas associated with reward and motivation (Albers, 2012, 2015; Caldwell & Albers, 2016; Gordon et al., 2011; Newman, 1999; O’Connell & Hofmann, 2011a), are of particular interest. It is also worth mentioning that the SBNN is not the only theoretical construct of what constitutes the “social brain,” although it is the one discussed in this article. To explore the relationship between the SBNN and the more neocortex-centric cognitive social brain theory of the “social brain,” see the recent paper by Prounis and Ophir (2020).

The Receptors

Oxytocin has one type of identified receptor, the oxytocin receptor (Oxtr), which transduces oxytocin’s signal in both the periphery and the brain. Vasopressin, on the other hand, has three identified receptors: the vasopressin 1a receptor (Avpr1a), the vasopressin 1b receptor (Avpr1b), and the vasopressin 2 receptor (Avpr2). Avpr1a and Avpr1b are found in the brain as well as the periphery, and Avpr2 is found only in the periphery. All of the receptors for oxytocin and vasopressin are G protein-coupled receptors (Dumais & Veenema, 2016; Freeman et al., 2017; Roper et al., 2011; Smith et al., 2017; Veinante & Freund-Mercier, 1997).

Oxytocin and vasopressin often have specific physiological and behavioral effects via their individual receptors (Carter et al., 2008; Heinrichs et al., 2009; Legros, 2001; Song & Albers, 2018; Stoop, 2012; Viviani & Stoop, 2008). However, due to the structural similarities of the receptors, with an approximate 25% alignment of the whole sequence across the four receptor genes (Gimpl & Fahrenholz, 2001; Manning et al., 2012; Maybauer et al., 2008), there is known to be cross-talk between the systems (Sala et al., 2011; Schorscher-Petcu et al., 2010; Song & Albers, 2018). Perhaps this is not surprising given that oxytocin and vasopressin have similar affinities for the Oxtr, the Avpr1a, and the Avpr1b in rats and mice (Manning et al., 2008, 2012). That said, it does make understanding the nuanced roles of these neuropeptides more challenging (see Smith et al., 2019).

Generally speaking, oxytocin and vasopressin receptors are distributed within structures of the SBNN and the mesolimbic dopamine system, both of which are important for social motivation and displays of social behaviors (reviewed in Caldwell & Albers, 2016). In primates, however, Oxtr expression is somewhat species-specific, as well as more localized, than what is observed in rodent species (Freeman et al., 2014; Loup et al., 1991; Schorscher-Petcu et al., 2009). While Oxtr expression in rodents is particularly prevalent in brain regions important for the processing of olfactory information, in primates, Oxtr are most often expressed in brain regions important to modulating the attention to social stimuli (see reviews by Freeman & Young, 2016; Putnam et al., 2018). However, in primates vasopressin receptors are expressed more widely or they are more detectable, including in the amygdala and cortex (Freeman et al., 2017; Schorscher-Petcu et al., 2009; Wang et al., 1997; Young et al., 1999). Brain regions that are considered part of the SBNN include the lateral septum, bed nucleus of the stria terminalis, medial amygdala, preoptic area, anterior hypothalamus, ventromedial hypothalamus, and periaqueductal gray (Newman, 1999). Brain regions that are a part of the mesolimbic dopamine system include prefrontal cortex, striatum, nucleus accumbens, ventral pallidum, hippocampus, lateral septum, bed nucleus of the stria terminalis, basolateral amygdala, and the ventral tegmental area (reviewed by Love, 2014). Note that there is overlap in several brain regions between the SBNN and the mesolimbic dopamine system (i.e., lateral septum, bed nucleus of the stria terminalis, and amygdala). It is hypothesized that the SBNN and the mesolimbic dopamine system actively interact with one another to allow an animal to make decisions in the context of motivated social behaviors. Thus, they can be considered together as part of a larger social decision-making network (O’Connell & Hofmann, 2011a, 2011b). This assertion is supported by extensive evidence demonstrating that the oxytocin system and the dopamine system interact with one another in several brain regions to directly modulate behavior (Borland et al., 2018; Hung et al., 2017; Liu & Wang, 2003; Peris et al., 2017; Schorscher-Petcu et al., 2010; Skuse & Gallagher, 2008; Smeltzer et al., 2006; Young et al., 2014). The importance of this convergence of information cannot be understated, as this is where individual personality and context collide to shape behavioral output in a broader social context.

Oxytocin, Vasopressin, and the Neural Regulation of Social Behaviors

In order to consider the diverse ways that oxytocin and vasopressin contribute to the neural regulation of social behavior, it is important to circle back to the idea of flexibility. Animals need to have flexibility in their behavioral responses, and it is likely that this flexibility is reflected in the underlying neural circuitry. Thus, the framework for the discussion here is that oxytocin’s and vasopressin’s effects on social behaviors are mediated by the emergent properties of the aforementioned social decision-making network, which would be rooted in the unique patterns of activity across neuroanatomical areas, resulting in individualized behavioral responses. For this to occur, at the very least, there would need to be integration of information associated with an individual’s internal state, including their personality and previous experience, as well as the external conditions, such as social context (O’Connell & Hofmann, 2012). It is within this framework that the effects of oxytocin and vasopressin are best considered. That is, broadly, how the two nonapeptides may contribute to social behaviors associated with the one, the few, or the many (Figure 1).

Figure 1. A schematic of the various levels of social behavior that are influenced by the oxytocin and vasopressin systems. At the individual level, genetic differences in the oxytocin and vasopressin systems are known to affect aspects of personality and temperament, which will in turn alter an individual’s evaluation of their behavioral context. Oxytocin and vasopressin are well known for their neuromodulatory effects on numerous aspects of social interactions, including social recognition memory, cooperative behaviors, and competitive behaviors, although their effects are often species-, sex-, brain region-, and context-specific. Beyond small-group interactions, in some species oxytocin and vasopressin may help to support behaviors that are important to large-group cooperativity, including behavioral synchrony and responsiveness.

The Individual—The One

An individual’s personality, temperament, or individual coping style shifts their processing of, and response to, social cues. While personality is studied extensively in humans, in nonhuman animals, with the notable exception of work in rhesus monkeys (see Altschul et al., 2019; Capitanio, 2011; Capitanio et al., 2004; Weinstein & Capitanio, 2008), far less is known about how personality, or variations in individual social phenotype, result in an individual’s response. However, seminal work in prairie voles has demonstrated that variations in Avpr1a expression, stemming from a combination of genetic and epigenetic effects, are associated with shifts in social monogamy (Donaldson & Young, 2013; Hammock et al., 2005; Hammock & Young, 2004, 2005; Ophir et al., 2008).

The data to support a role for oxytocin and vasopressin in individual personality are perhaps most compelling in primates. Genetic variations, such as single nucleotide polymorphisms (SNPs) or microsatellite sequences in the 5′ flanking region of oxytocin and vasopressin receptors, are associated with variations in behavioral phenotype in bonobos, chimpanzees, marmoset, and humans (Hopkins et al., 2012; Inoue-Murayama et al., 2018; Meyer-Lindenberg et al., 2009; Rosso et al., 2008; Skuse et al., 2014; Staes et al., 2014, 2015). As an example, in humans, SNPs in the OXTR and AVPR1A genes are predictive of particular personality traits (Bakermans-Kranenburg & van Ijzendoorn, 2008; Meyer-Lindenberg et al., 2009; Rodrigues et al., 2009; Tost et al., 2010; Wu et al., 2005), including emotional arousal (Meyer-Lindenberg et al., 2009), empathic capacity (Bakermans-Kranenburg & van Ijzendoorn, 2008; Rodrigues et al., 2009; Tost et al., 2010), and social behavior (Lucht et al., 2009; Skuse et al., 2014; Walum et al., 2012). AVPR1A polymorphisms have been linked to personality traits ranging from creative dance and interest in music (Bachner-Melman et al., 2005; Ukkola-Vuoti et al., 2011) to affiliative traits (Meyer-Lindenberg et al., 2009; Prichard et al., 2007; Walum et al., 2008). There are also data to suggest that SNPs in AVPR1A correlate with personality-associated (i.e., extraversion versus introversion) differences in amygdala activation (Andari et al., 2014). Taken together, the data support the notion that the oxytocin and vasopressin systems contribute to aspects of personality across vertebrate species. While the data are complex, and somewhat limited in nonhuman animals, this work has provided critical insights into some of the mechanisms that contribute to an individual’s behavior.

Interactions Among Individuals—The Few

Oxytocin and vasopressin contribute to three important aspects of social behavior, specifically, social recognition memory, cooperative behaviors, and competitive behaviors. Even though social interactions are not compartmentalized in this way, these categories reflect the way that the behaviors are often studied. That said, all three aspects are at the core of many social interactions, although the extent to which they are displayed by individual species can vary widely.

Social Recognition Memory

Social recognition memory allows individuals to identify their mates and family members or to recognize that they are meeting someone new. Thus, social recognition memory provides important contextual information that helps determine an individual’s behavioral response. For instance, the decision to approach or to avoid another individual will be affected by your memory, or lack of memory, of that individual.

In rodents, both oxytocin and vasopressin contribute to different aspects of social recognition memory, in brain region-specific ways (Caldwell, 2017; Gabor et al., 2012; Lee et al., 2009; Smith et al., 2016; Song et al., 2016; Wacker & Ludwig, 2012). For instance, oxytocin knockout (Oxt −/−; Ferguson et al., 2000) mice and Oxtr knockout (Oxtr −/−) mice, including forebrain-specific Oxtr knockout (Oxtr FB/FB) mice, all have deficits in social recognition memory (Ferguson et al., 2000; Hattori et al., 2015; Lee, Caldwell, Macbeth, Tolu et al., 2008; Lee, Caldwell, Macbeth, & Young, 2008; Macbeth et al., 2009; Takayanagi et al., 2005). In the case of Oxt −/− mice, the observed “social amnesia” phenotype can be reversed if oxytocin is infused into the medial amygdala prior to memory acquisition (Ferguson et al., 2000, 2001). Within regions of the hippocampus, oxytocin signaling is important to pattern separation, which aids in social discrimination (Raam et al., 2017). In the olfactory system, oxytocin infused into the olfactory bulb or optogenetic simulation of oxytocin release in the anterior olfactory nucleus, which has projections to the olfactory bulb, can affect social recognition memory. The former facilitates social memory (Benelli et al., 1995; Dluzen et al., 1998) and the latter appears to enhance the signal-to-noise ratio of social olfactory cues and in turn increase social recognition memory (Oettl et al., 2016). There is also evidence for crosstalk between the oxytocin and vasopressin systems in this domain. In Syrian hamsters, central administration of either oxytocin or vasopressin can extend social memory, but these effects are solely mediated by the Oxtr (Song et al., 2016).

In the case of vasopressin, there are androgen-dependent vasopressin projections from the medial amygdala and the bed nucleus of the stria terminalis to the lateral septum, all parts of the SBNN, which are known to be important for individual recognition (Bluthe et al., 1990, 1993; De Vries et al., 1984; Mayes et al., 1988; Rigney et al., 2019). Vasopressin in both the lateral septum and the hippocampus affects social recognition memory. In the lateral septum, vasopressin facilitates social memory (Engelmann & Landgraf, 1994; Everts & Koolhaas, 1999; Landgraf et al., 1995), and in the hippocampus, infusion of an Avpr1b antagonist into the CA2 region, prior to acquisition, prevents the formation of social memory (Smith et al., 2016). There is also evidence that vasopressin in the olfactory bulb is important for the processing of olfactory information (Tobin et al., 2010), similar to what is observed with oxytocin (Benelli et al., 1995; Dluzen et al., 1998).

Even in humans, there is evidence that oxytocin and vasopressin may be important to social recognition memory. Intranasal oxytocin has been hypothesized to improve the neural coding (Guastella et al., 2008; Heinrichs et al., 2004) and recall of positive socially salient information (Tse et al., 2018), which is consistent with some work in rodents (Oettl et al., 2016). While data on the vasopressin system and social recognition memory are scant, intranasal vasopressin does appear to enhance the coding of happy as well as angry faces (Guastella et al., 2010), both of which are important cues for appropriate social interactions. Although the brain areas where oxytocin and vasopressin signal to alter human social recognition memory are unknown, these neuropeptides do appear to be involved in this aspect of behavior across species, independent of the sensory modality. It is important to remember that recognition memory is evolutionarily advantageous, because it helps an animal make decisions about whether cooperative or competitive behaviors should be displayed.

Cooperative Behaviors

Cooperative behaviors include interactions ranging from the pair bond, which is formed between a male and a female in a reproductive context, to friendships. With respect to the pair bond, our understanding of oxytocin and vasopressin’s contributions comes primarily from work in prairie voles. The literature in this area is deep and is reviewed elsewhere (Caldwell & Albers, 2016; Tabbaa et al., 2016; Walum & Young, 2018). Briefly, the systematic study of vole species that are socially monogamous (prairie or pine voles) and those that are socially promiscuous (montane or meadow voles) has resulted in important insights into how oxytocin and vasopressin contribute to differences in social behavior (reviewed in Walum & Young, 2018). From these studies, the nucleus accumbens has emerged as a brain area where oxytocin signaling affects pair bond formation in prairie voles (Keebaugh et al., 2015; Liu & Wang, 2003; Ross et al., 2009; Young et al., 2001). For vasopressin, Avpr1a signaling in the ventral pallidum is important, because its expression in the promiscuous meadow vole can facilitate the formation of a pair bond (Lim et al., 2004). More recently, the pair bond model has been extended to titi monkeys (Callicebus cupreus; Bales et al., 2017). Thus far, data from this species suggest that oxytocin and vasopressin receptors are expressed in brain regions important to the processing of visual and olfactory stimuli (Freeman et al., 2014). Further, intranasal administration of vasopressin to male titi monkeys affects approach behaviors (Jarcho et al., 2011).

Beyond pair bonding and parental behavior, nonreproductive social bonds are less studied, probably because they are more nuanced. However, evidence of a role for oxytocin and vasopressin in nonreproductive social bonds comes from numerous sources. In domestic dogs, intranasal oxytocin increases social play behavior (Romero et al., 2015), and oxytocin may promote a social bond between dogs and humans (Marshall-Pescini et al., 2019); although, the neurochemical underpinnings of this bond have yet to be explored. In rhesus macaques, friendships predict later concentrations of plasma oxytocin and vasopressin in sex- and friendship-specific ways (Weinstein et al., 2014). In humans, oxytocin also appears to be important in nonreproductive bonds. For example, intranasal oxytocin treatment can increase ingroup cooperation (and sometimes competition between groups) (De Dreu, 2012; Ma et al., 2015; Stallen et al., 2012), trust (reviewed in Van & Bakermans-Kranenburg, 2012), and social approach (Cohen et al., 2018; Cohen & Shamay-Tsoory, 2018). A recent imaging study found that intranasal oxytocin decreases brain activity in the amygdala and insula of women, but not men, when they share with friends. This change in brain activity is hypothesized to be due, at least in part, to the anxiety-reducing effects of oxytocin (Ma et al., 2018). At this time, the only empirical study linking vasopressin to nonreproductive social bonds in humans is a polymorphism in AVPR1A that is associated with trust behavior (Knafo et al., 2008).

Competitive Behaviors

Competitive behaviors are important to social interactions and are often intertwined with cooperative behaviors. For example, the formation of dominance relationships is pervasive in the animal kingdom and often results in a reduction in social conflict (Alexander, 1974). Further, competitive behaviors can define the boundaries between an ingroup and an outgroup. It is also important to consider that not all competitive behaviors are associated with overt displays of aggression. Rather, there are numerous other ways by which animals set personal boundaries, including scent marking, vocalizations, and dominance, all of which are known to be modulated by oxytocin and vasopressin (Albers et al., 2002; Fernald, 2014; Freeman et al., 2018). For a more comprehensive review of this topic, see Caldwell and Albers (2016).

In rodents, oxytocin appears to have largely anti-aggressive effects in adult males (Calcagnoli et al., 2013, 2014; Calcagnoli, Kreutzmann et al., 2015; Calcagnoli, Stubbendorff et al., 2015). Work in squirrel monkeys and female hamsters suggests that oxytocin’s effects on aggressive/agonistic behaviors depends on an individual’s social status (Harmon et al., 2002; Winslow & Insel, 1991). In fact, it is a recurring theme that oxytocin’s and vasopressin’s effects on aggressive and agonistic behaviors are often dependent upon an individual’s social status and/or their social experience (see Albers et al., 2006; Caldwell & Albers, 2004; Michopoulos et al., 2011, 2012; Timmer et al., 2011). There is also evidence that oxytocin can affect maternal aggression (see reviews by Bosch, 2013, and Leng et al., 2008).

With respect to vasopressin, there is fairly compelling evidence that, at least in males, that aggressive behavior is facilitated via vasopressin’s action on both the Avpr1a and the Avpr1b (for review, see Terranova et al., 2017). Avpr1a activation in the anterior hypothalamus (Caldwell & Albers, 2004; Ferris et al., 1997; Ferris & Potegal, 1988; Gobrogge et al., 2007; Potegal & Ferris, 1989), ventrolateral hypothalamus (Delville et al., 1996), and lateral septum (Beiderbeck et al., 2007) are particularly important for the facilitation of aggressive behavior in numerous species. In contrast, in female Syrian hamsters, activation of the Avpr1a inhibits offensive aggressive behavior (Gutzler et al., 2010; Terranova et al., 2016).

Unlike the Avpr1a, the Avpr1b is more discretely localized in the brain (Lolait et al., 1995; Young et al., 2006), and signaling through this receptor in the CA2 region of the hippocampus is critical for displays of aggressive behavior (Pagani et al., 2015). While Avpr1a may be more involved in the modulation of aggression and agonistic behaviors in key hypothalamic sites, Avpr1b is important for helping an animal determine its social context by increasing the social salience of the signal; this is consistent with its role in social recognition memory (Smith et al., 2016).

Since oxytocin and vasopressin do not cause behaviors to occur, but rather have nuanced effects that are moderated by many factors, it is perhaps not surprising that the data from humans with respect to competitive behaviors are not particularly consistent with the findings in non-human mammals. Researchers have evaluated peripheral oxytocin and vasopressin concentrations in healthy young males and have found no associations with aggressive behaviors (Berends, Tulen, Wierdsma, van Pelt, Kushner et al., 2019); although, intranasal oxytocin does appear to increase aggressive responses in a task-related test (Berends, Tulen, Wierdsma, van Pelt, Feldman et al., 2019). Most of the work in humans suggests that oxytocin and vasopressin more broadly affect aspects of social cognition, such as trust and ingroup favoritism.

While this section covers important social behaviors that are mediated by oxytocin and vasopressin, a great deal of information has been excluded, including the developmental origins of these systems and how they may affect the underlying neural circuits that regulate social behaviors (Cushing, 2013; Hammock, 2015; Kenkel et al., 2019b; Miller & Caldwell, 2015), how these behaviors are altered by experience (Bales & Perkeybile, 2012; Carter, 2017; Perkeybile & Bales, 2017; Perkeybile et al., 2019), how they change as a function of age (Bredewold & Veenema, 2018; Kenkel et al., 2019a), and how they differ by sex (Borland et al., 2019; Caldwell, 2018; Dumais & Veenema, 2016).

Group Cooperation—The Many

Compared to our understanding of interactions among individuals, far less is known or understood about the contributions of oxytocin and vasopressin to group cooperative behaviors. With respect to oxytocin, De Dreu and Kret (2016) hypothesize that, by increasing the salience of social cues, individuals shift from a self- to a group-focus, which is more permissive for group-based decision-making. It is already established that certain species, or individuals within a species, have the type of temperament/personality that is more compatible with group cooperative behavior. So, while the neural underpinnings of group cooperation are poorly understood, it does seem that oxytocin and vasopressin have roles to play at the level of the individual, one-on-one interactions, and the group.

Evidence that oxytocin may be important to group living can be found in wild chimpanzees and common marmosets. Wild chimpanzees live in large social groups and have elevated urinary oxytocin after sharing of food resources that were either jointly or individually obtained (Samuni et al., 2018; Wittig et al., 2014) or after bouts of grooming (Crockford et al., 2013). In group-living common marmosets, urinary oxytocin is synchronized between pairs of individuals and has long-term stability (Finkenwirth & Burkart, 2017). Thus, it appears that oxytocin may help to promote long-term social bonds between kin and non-kin individuals, which is critical for long-term cooperative relationships between individuals of a group. Kasper and colleagues (2017) suggest that three cognitive skills are required for cooperative living: event memory, synchrony with others, and responsiveness to others. Based on the data from humans and nonhuman primates, as well as work in some group-living rodents, it does appear that oxytocin helps to modulate behavioral synchrony and responsiveness to others.

Conclusion

Research on oxytocin and vasopressin and the neural regulation of social behavior suggests that both nonapeptides contribute to aspects of an individual’s personality, interactions between a few individuals, and group cooperation. While work much of the research has focused predominantly on interactions between a few, usually two, individuals, more researchers are now exploring how the oxytocin and vasopressin systems may shape individual behavioral phenotypes as well as cooperative behaviors in larger group settings. When considered together, the data suggest that these systems have evolved to support all aspects of social living. Ultimately, while much more work is needed unravel the complexity of these systems, the insights that will be gained from these efforts will likely have sweeping implications for all species.

Acknowledgments

The author thanks Elizabeth Aulino and Dr. Colleen Novak for their comments on this manuscript. The author is supported by NIH grant HD090606.

References