Oxytocin modulates mate-guarding behavior in marmoset monkeys.

In socially-monogamous species, intolerance of interactions between a pairmate and a sexual rival (i.e., mate-guarding) promotes the preservation of long-lasting partnerships. One promising neurobiological candidate for the regulation of mate-guarding behavior in monogamous primates is the oxytocin (OT) system, given its established role in both the development of monogamous bonds and the behavioral processes that facilitate the preservation of those bonds. In this study, male and female marmosets were exposed to a same-sex intruder in their home environment during conditions when their pairmate was present and absent, and across three treatment conditions (OT receptor agonist; saline control; OT receptor antagonist). Saline-treated marmosets spent significantly more time in proximity to the intruder, relative to the empty pairmate enclosure, when their pairmate was absent. However, when marmosets received OT they spent less time in proximity to the intruder, indicating that OT may reduce interest in a same-sex stranger in a territorial context. When their pairmate was present, saline-treated marmosets spent equal time in proximity to both intruder and pairmate; yet when they received OT they spent significantly more time in proximity to the intruder, indicating that OT may increase interest in a same-sex stranger in a mate-guarding context. While OT treatment did not directly influence the expression of aggression, OT system manipulations impacted the expression of selective social interest during an intruder challenge, suggesting that OT may enhance adaptive responses to social challenges. Moreover, these findings add to the converging evidence that the OT system regulates behavioral processes that underlie the preservation of established relationships.

Oxytocin regulates reunion affiliation with a pairmate following social separation in marmosets.

While separation from significant social partners produces a host of neurobiological and behavioral perturbations, including behavioral distress and increased glucocorticoid production, positive social interactions upon reunion are critical for the reestablishment of normative relationship dynamics and the attenuation of the biobehavioral stress response. The hormone oxytocin has critical and pervasive roles in reproductive and behavioral processes across the lifespan, and plays a particularly prominent role in social bonding. In this study, we examined the extent that oxytocin modulates interactions with a pairmate following separation challenges that varied in both social context (isolation; separation) and duration (long; short), in marmosets. We demonstrated that the impact of pharmacological manipulations of the oxytocin system on the expression of affiliation upon reunion depended on both the context and duration of the separation challenge. Specifically, marmosets treated with an oxytocin antagonist spent less time in proximity with their pairmate upon reunion following a long-separation challenge. During the short-separation challenge, marmosets engaged in more social gaze when separated with an opposite-sex stranger, but not when separated with their mate. Furthermore, marmosets that received the most social gaze from opposite-sex strangers spent the most time in proximity with their long-term mate upon reunion. We also showed that marmosets treated with an OT agonist received increased levels of gaze from opposite-sex strangers, but not from their mate. Overall, these results suggest that marmosets are sensitive to the nature of the social interactions during separation, and subsequently alter their expression of affiliation upon reunion with their long-term mate. These findings further implicate oxytocin as a bond-enhancing molecule that regulates the reestablishment of normative levels of affiliation with a mate following separation, and add to the emerging literature that suggests the OT system underlies critical behavioral processes that contribute to the preservation of long-lasting social bonds.

Neuropeptide diversity and the regulation of social behavior in New World primates.

Oxytocin (OT) and vasopressin (AVP) are important hypothalamic neuropeptides that regulate peripheral physiology, and have emerged as important modulators of brain function, particularly in the social realm. OT structure and the genes that ultimately determine structure are highly conserved among diverse eutherian mammals, but recent discoveries have identified surprising variability in OT and peptide structure in New World monkeys (NWM), with five new OT variants identified to date. This review explores these new findings in light of comparative OT/AVP ligand evolution, documents coevolutionary changes in the oxytocin and vasopressin receptors (OTR and V1aR), and highlights the distribution of neuropeptidergic neurons and receptors in the primate brain. Finally, the behavioral consequences of OT and AVP in regulating NWM sociality are summarized, demonstrating important neuromodulatory effects of these compounds and OT ligand-specific influences in certain social domains.

Neonatal oxytocin and vasopressin manipulation alter social behavior during the juvenile period in Mongolian gerbils.

Oxytocin and vasopressin are important modulators of a wide variety of social behaviors, and increasing evidence is showing that these neuropeptides are important organizational effectors of later-life behavior as well. We treated day-old gerbil pups with oxytocin, vasopressin, an oxytocin receptor antagonist, a vasopressin V1a receptor antagonist, or saline control, and then measured received parental responsiveness during the early postnatal period and juvenile social behavior during weaning. Neonatal vasopressin treatment enhanced sociality in males, but not females, at both developmental time points. When pups were individually placed outside the nest, parents were more responsive to male pups treated with vasopressin compared with littermates, and vasopressin treated male pups exhibited increased play with littermates as juveniles. These results show that vasopressin during very early life can enhance social interactions throughout early development.

Do marmosets care to share? Oxytocin treatment reduces prosocial behavior toward strangers.

Cooperatively-breeding and socially-monogamous primates, like marmosets and humans, exhibit high levels of social tolerance and prosociality toward others. Oxytocin (OXT) generally facilitates prosocial behavior, but there is growing recognition that OXT modulation of prosocial behavior is shaped by the context of social interactions and by other motivational states such as arousal or anxiety. To determine whether prosociality varies based on social context, we evaluated whether marmoset donors (Callithrix penicillata) preferentially rewarded pairmates versus opposite-sex strangers in a prosocial food-sharing task. To examine potential links among OXT, stress systems, and prosociality, we evaluated whether pretrial cortisol levels in marmosets altered the impact of OXT on prosocial responses. Marmosets exhibited spontaneous prosociality toward others, but they did so preferentially toward strangers compared to their pairmates. When donor marmosets were treated with marmoset-specific Pro(8)-OXT, they exhibited reduced prosociality toward strangers compared to marmosets treated with saline or consensus-mammalian Leu(8)-OXT. When pretrial cortisol levels were lower, marmosets exhibited higher prosociality toward strangers. These findings demonstrate that while marmosets show spontaneous prosocial responses toward others, they do so preferentially toward opposite-sex strangers. Cooperative breeding may be associated with the expression of prosociality, but the existence of a pair-bond between marmoset partners appears to be neither necessary nor sufficient for the expression of spontaneous prosocial responses. Furthermore, high prosociality toward strangers is significantly reduced in marmosets treated with Pro(8)-OXT, suggesting that OXT does not universally enhance prosociality, but, rather OXT modulation of prosocial behavior varies depending on social context.

Post-partum variation in the expression of paternal care is unrelated to urinary steroid metabolites in marmoset fathers.

The organization and activation of maternal care are known to be highly regulated by hormones and there is growing evidence that expression of paternal care is also related to endocrine substrates. We examined the relationship between paternal behavior and steroid hormones in marmoset fathers (Callithrix geoffroyi) and evaluated whether hormone-paternal behavior relationships were altered by previous offspring-care experience in males. Based on previous findings, we predicted that testosterone, estradiol, and cortisol would decrease following the birth of offspring and would be lowest during the period of maximal infant carrying. Furthermore, we predicted that post-partum changes in carrying effort and hormone levels would be influenced by the level of offspring-care experience. Carrying effort and other paternal care behaviors underwent temporal changes over the post-partum period, but these patterns were not related to variation in hormone concentrations over the same period. There was a limited effect of offspring-care experience on hormone concentrations, but experience was found to play a role in the expression of paternal care, with experienced fathers engaging in significantly more infant allogrooming than inexperienced fathers. Furthermore, inexperienced fathers increased the frequency of food sharing in response to infant begging across the post-partum period, while experienced fathers displayed consistently low levels. We posit that a combination of experiential factors and an increased role for alloparents in offspring-care led to these changes. However, it appears that hormonal changes may not influence paternal responsiveness in white-faced marmoset fathers and that hormone-paternal behavior relationships are not critically dependent on a male's previous offspring-care experience.

Social Monogamy in Nonhuman Primates: Phylogeny, Phenotype, and Physiology.

Monogamy as a social system has been both a scientific puzzle and a sociocultural issue for decades. In this review, we examine social monogamy from a comparative perspective with a focus on primates, our closest genetic relatives. We break down monogamy into component elements, including pair-bonding and partner preference, mate guarding or jealousy, social attachment, and biparental care. Our survey of primates shows that not all features are present in species classified as socially monogamous, in the same way that human monogamous relationships may not include all elements-a perspective we refer to as "monogamy à la carte." Our review includes a survey of the neurobiological correlates of social monogamy in primates, exploring unique or common pathways for the elemental components of monogamy. This compilation reveals that the components of monogamy are modulated by a suite of androgenic steroids, glucocorticoid hormones, the nonapeptide hormones oxytocin and vasopressin, and other neurotransmitter systems (e.g., dopamine and opioids). We propose that efforts to understand the biological underpinnings of complex human and animal sociosexual relationships will be well served by exploring individual phenotypic traits, as opposed to pursuing these questions with the assumption that monogamy is a unitary trait or a species-specific characteristic.

Oxytocin modulates behavioral and physiological responses to a stressor in marmoset monkeys.

Social isolation is a major source of stress and can lead to activation of the hypothalamic-pituitary-adrenal (HPA) axis. The presence of a close social partner can reduce the magnitude of the HPA-axis response during a stressor, a phenomenon known as social buffering. The oxytocin (OXT) system has been identified as one candidate for mediating social buffering due to its role in the facilitation of social bonding and the expression of prosocial behavior. The goal of the present study was to determine whether the OXT system contributes to social buffering of HPA-axis activity in response to stressor exposure in marmoset monkeys (Callithrix jacchus). Male and female marmosets experienced a standardized psychogenic stressor with and without their long-term mate under OXT-treatments (Pro(8)-OXT, Leu(8)-OXT, OXT antagonist, and saline); we assessed HPA-axis activity by measuring urinary cortisol across the stressor. We found that blocking, but not augmenting, the OXT system altered patterns of cortisol and proximity behavior in response to a stressor. We demonstrated that (1) the presence of a mate during a stressor significantly attenuated HPA-axis activity in female, but not male, marmosets; (2) male, but not female, marmosets treated with an OXT antagonist had significantly higher HPA-axis activity across the stressor than when they were treated with saline, suggesting that the OXT system may reduce the stressor-induced rise in cortisol levels; (3) male and female marmosets treated with an OXT antagonist spent significantly less time in close proximity to their mate during the first 30 min of the stressor than when they were treated with saline, suggesting that the OXT system may be important for the expression of partner-seeking behavior during a stressor. Thus, the OXT system and social context differentially influenced how the HPA-axis responded to a stressor in male and female marmosets, and may modulate HPA-axis activity by promoting the expression of proximity behavior with a close social partner.

Gene changes may minimize masculinizing and defeminizing influences of exposure to male cotwins in female callitrichine primates.

BACKGROUND: Sexual differentiation in female mammals can be altered by the proximity of male littermates in utero, a phenomenon known as the intrauterine position effect (IUP). Among simian primates, callitrichines (marmosets and tamarins) are likely candidates for IUP, since they exhibit obligate dizygotic twinning and fetuses share extensive vascularization in utero. In this paper, we determined whether female reproductive parameters are altered by gestating with a male twin and evaluated changes in genes associated with anti-Müllerian and steroid hormones in twinning callitrichine primates. METHODS: We assessed the impact of gestation with male cotwins on reproductive performance and survivorship in female marmosets (Callithrix) and lion tamarins (Leontopithecus), contrasting measures for females gestated with one or more littermates (M+) or no male littermates (0M). We compared targeted coding regions for genes involved in steroidal and anti-Müllerian hormone mediation of sexual differentiation for representatives of twinning callitrichines (Callithrix, Saguinus, and Leontopithecus) with closely related New World primates that produce single births (Saimiri and Callimico). RESULTS: IUP effects in females were absent in female callitrichine primates: age at first ovulation, average litter size, and the proportion of stillborn infants, and lifetime survivorship did not differ between M+ and 0M females. We documented multiple nonsynonymous substitutions in genes associated with steroid synthesis, transport, and cellular action (SRD5A2, CYP19A1, SHBG, and AR) and with anti-Müllerian hormone (AMH and AMHR2) in callitrichines. In the only callitrichine to produce single infants (Callimico), two genes contained nonsynonymous substitutions relative to twinning callitrichines (CYP19A1 and AMRHR2); these substitutions were identical with nontwinning Saimiri and humans, suggesting a reversion to an ancestral sequence. CONCLUSIONS: In spite of a shared placental vasculature with opposite-sex twins throughout embryonic and fetal development, female callitrichine primates gestated with a male cotwin exhibit no decrement in reproductive performance relative to females gestated with female cotwins. Hence, IUP effects on female reproduction in callitrichines are modest. We have identified mutations in candidate genes relevant for steroid hormone signaling and metabolism, and especially in AMH-related genes, that are likely to alter protein structure and function in the callitrichines. These mutations may confer protection for females from the masculinizing and defeminizing influences of gestating with a male cotwin.

Inequity aversion strategies between marmosets are influenced by partner familiarity and sex but not oxytocin.

Cooperation among individuals depends, in large part, on a sense of fairness. Many cooperating non-human primates (NHPs) show inequity aversion, (i.e., negative responses to unequal outcomes), and these responses toward inequity likely evolved as a means to preserve the advantages of cooperative relationships. However, marmosets (Callithrix spp.) tend to show little or no inequity aversion, despite the high occurrence of prosociality and cooperative-breeding in callitrichid monkeys. Oxytocin [OXT] has been implicated in a wide variety of social processes, but little is known about whether OXT modulates inequity aversion toward others. We used a tray pulling task to evaluate whether marmosets would donate superior rewards to their long-term pairmate or an opposite-sex stranger following OXT, OXT antagonist, and saline treatments. We found that marmosets show inequity aversion, and this inequity aversion is socially- and sex-specific. Male marmosets show inequity aversion toward their pairmates but not strangers, and female marmosets do not show inequity aversion. OXT treatments did not significantly influence inequity aversion in marmosets. While OXT may modulate prosocial preferences, the motivations underlying cooperative relationships, such as inequity aversion, are multifaceted. More research is needed to evaluate the evolutionary origins, biological processes, and social contexts that influence complex phenotypes like inequity aversion. Inequity aversion can differ within species in important and distinct ways including between individuals who do and do not share a cooperative relationship. Overall, these findings support the view that inequity aversion is an important behavioural strategy for the maintenance of cooperative relationships.

Marmosets treated with oxytocin are more socially attractive to their long-term mate.

Adult male-female bonds are partly characterized by initiating and maintaining close proximity with a social partner, as well as engaging in high levels of affiliative and sociosexual behavior. Oxytocin (OXT), a neuromodulatory nonapeptide, plays a critical role in the facilitation of social bonding and prosocial behavior toward a social partner (Feldman, 2012). However, less attention has been given to whether augmentation of OXT levels in an individual alters others' perceptions and behavior toward an OXT-treated social partner. We examined social dynamics in well-established male-female pairs of marmoset monkeys (Callithrix jacchus) in which one member of the pair was administered an intranasal OXT agonist, an OXT antagonist (OXTA), or saline. OXT treatment did not alter the expression of affiliative toward an untreated partner. However, OXT did significantly influence the expression of proximity and grooming behavior with a treated partner, as a function of OXT treatment and sex. Female interest in initiating and maintaining proximity with a pair-mate was altered by OXT treatment. Untreated female marmosets departed from their saline-treated partner more frequently than they approached them, as indicated by a low proximity index score. However, when males received an intranasal OXT agonist they had a significantly increased proximity index score relative to saline, indicating that their untreated partner approached them more often than they departed from them). Saline-treated females initiated and received equivalent levels of grooming behavior. However, when female marmosets were treated with an OXT agonist their untreated partner groomed them proportionately more often, for a greater total duration, and for more time per bout, than they initiated grooming behavior. These results suggest that intranasal OXT altered male and female marmosets' stimulus properties in such a way as to increase the amount of grooming behavior that females received from their long-term mate, as well as increase female interest in initiating and maintaining proximity with their long-term mate. Furthermore, these results support the notion that central OXT activity plays an important neuromodulatory role in the maintenance of long-lasting male-female relationships.

Oxytocin facilitates fidelity in well-established marmoset pairs by reducing sociosexual behavior toward opposite-sex strangers.

Behavioral strategies that facilitate the maintenance of social bonds are critical for the preservation of high-quality social relationships. Central oxytocin (OT) activity modulates the behavioral features of socially monogamous relationships in a number of mammalian species (including marmoset monkeys), and plays a vital role in the behavioral maintenance of long-term social relationships. Two distinct variants of OT have been identified in some New World primates (including marmosets; Lee et al., 2011). The marmoset variant of the oxytocin ligand (Pro(8)-OT) is structurally distinct from the consensus mammalian variant of the oxytocin ligand (Leu(8)-OT), due to a proline substitution at the 8th amino-acid position. The goal of the present study was to determine if treating marmosets with Pro(8)-OT, relative to treatments with Leu(8)-OT, control saline, or an OT antagonist, had modulatory effects on the behavioral maintenance of long-term social relationships in marmosets. Treatment with the Pro(8) variant, but not the Leu(8) variant, of OT facilitated fidelity with a long-term partner by reducing time spent in close proximity with an opposite-sex stranger. However, this facilitative effect of Pro(8)-OT on proximity behavior manifested itself differently in male and female marmosets, such that females preferred to interact socially with their partner rather than a stranger when treated with Pro(8)-OT, while males spent less time in close proximity with both their partner and a stranger when treated with Pro(8)-OT. Furthermore, treatment with Pro(8)-OT, but not Leu(8)-OT, significantly delayed the expression of sexual solicitation behavior toward an opposite-sex stranger in both male and female marmosets, but had no effect on sociosexual behavior directed toward a long-term partner. These results suggest that the OT system is highly involved in reducing fidelity-threatening behaviors in well-established marmoset pairs, and that the effects were only produced by species-specific OT ligands.

Quality of maternal and paternal care predicts later stress reactivity in the cooperatively-breeding marmoset (Callithrix geoffroyi).

Variation in the early postnatal social environment can have lasting effects on hypothalamic-pituitary-adrenal (HPA) axis stress responses. Both rats and macaque monkeys subjected to low quality or abusive maternal care during the early postnatal period have more pronounced HPA responses to environmental stressors throughout development and into adulthood compared to animals reared in higher quality early maternal environments. However, little is known about the relative contributions to HPA stress response styles in developing offspring in species in which offspring care is routinely provided by group members other than the mother, such as in cooperatively breeding mammals. Marmoset monkeys exhibit cooperative offspring rearing, with fathers and older siblings providing care in addition to that provided by the mother. We evaluated the effects of early maternal, paternal, and older sibling care on HPA responses to social separation across development in captive white-faced marmoset offspring (Callithrix geoffroyi). We monitored offspring care by mothers, fathers, and older siblings in marmosets for the first 60 days of life. Later in development, each marmoset experienced three standardized social separation/novelty exposure stressors at 6, 12, and 18 months of age. During separation, we collected urine samples and analyzed them via enzyme immunoassay for cortisol levels. Infants that received higher rates of rejections from the entire family group showed higher cortisol responses to social separation. This relationship was found when mothers, fathers, and older siblings, were analyzed separately as well. No differences in cortisol responses were found between offspring that received high and low rates of carrying or high and low rates of licking and grooming by any group member. In the cooperatively breeding marmoset, early social cues from multiple classes of caregivers may influence HPA stress responses throughout the lifespan.

The influence of androgenic steroid hormones on female aggression in 'atypical' mammals.

Dimorphism on dominance and agonistic behaviour in mammals tends to be strongly biased toward males. In this review, we focus on a select few species of mammals in which females are as or more aggressive than males, and/or are dominant to males, and explore the role of androgenic hormones in mediating this important difference. While the data are not as clear-cut as those published on traditional laboratory mammals, our review highlights important endocrine substrates for both organizational and activational influences of steroids on female aggressive behaviour. We highlight areas in which further observations and experiments are crucial, especially the potential facilitative effects of androgens on female aggression. Finally, new and innovative techniques, including molecular genetics and receptor pharmacology, portend important insights into the ways in which androgenic hormones regulate aggressive behaviour in 'atypical' female mammals.