It has become increasingly clear that the nonapeptide hormones oxytocin and vasopressin have more diverse behavioral and physiological effects across species and across individuals than was initially recognized. To reflect this variation, we would like to introduce our Special Issue, entitled Oxytocin and Vasopressin in Primate Behavior, by celebrating the diversity that is found across the articles within it. While every article directly addresses the topic of this Special Issue, they also vary in many characteristics: the species studied, the methods used, and the perspectives taken. By highlighting the interesting ways in which these articles differ from one another, we can gain unique insights into the subject that ties them together: our understanding of oxytocin and vasopressin and the behavior of primates. Nonhuman primates are critical intermediates between rodents and humans and are the best models for human biology and behavior, especially with respect to complex cognitive social constructs, such as visual social attention, face processing, and vocal communication. While rodent studies have laid an important and foundational framework for our understanding of nonapeptides, brains, and behavior, these studies cannot fully recapitulate human phenomena. Therefore, we hope the articles presented here contribute to a greater understanding on the role of oxytocin and vasopressin in primate physiology and behavior and help to further advance the application of this knowledge to human biology.

Two separate lines of research indicate (a) that prenatal stress is associated with heightened behavioral and physiological reactivity and (b) that these postnatal phenotypes are associated with increased susceptibility to both positive and negative developmental experiences. Therefore, prenatal stress may increase sensitivity to the rearing environment. We tested this hypothesis by manipulating prenatal stress and rearing-environment quality, using a cross-fostering paradigm, in prairie voles. Results showed that prenatally stressed voles, as adults, displayed the highest behavioral and physiological reactivity when cross-fostered to low-contact (i.e., low-quality) rearing but the lowest behavioral and physiological reactivity when cross-fostered to high-contact (i.e., high-quality) rearing; non-prenatally stressed voles showed no effect of rearing condition. Additionally, while neither prenatal stress nor rearing condition affected oxytocin receptor binding, prenatally stressed voles cross-fostered to high-contact rearing showed the highest vasopressin-1a receptor binding in the amygdala. Results indicate that prenatal stress induces greater environmental sensitivity, making it both a risk and an opportunity factor.

Highly valued food items are often used as rewards to reinforce an animal's behavior. For social species, social interaction is rewarding and can drive an individual's behavior as well. In the currently study, we wanted to compare the efficacy of a food reward and a social reward on object discrimination learning in socially monogamous titi monkeys. We hypothesized that titi monkeys would perform more accurately for a social reward (their pair mate) than for a food reward (a highly desired food item). Eleven adult titi monkeys were tested with a two-object visual discrimination task for both types of reward. The colors and shapes of the objects in the two-object discrimination task were counterbalanced across subjects. During each trial, subjects were shown two objects, and the trial ended when the subject touched the reinforced shape (S+) or after 5 min. A correct trial was defined as one when the subject touched S+ first. We found that 45.5% of subjects were able to learn the task with a social reward, and 83.3% were able to learn the task with a food reward. We found that subjects balked more often and had fewer correct trials for the social reward. Finally, subjects took longer to approach the shapes for a social reward, possibly indicating lower motivation to engage in the task when a social reward is used compared to a food reward. Although significantly fewer subjects met criteria of success with the social reward than with the food reward, our results show that titi monkeys can learn a visual discrimination task with either type of reward.

Early experience and social context interact to alter the phenotype of complex social behaviors. These early experiences can also result in alterations to cortical organization and connections. Given the ability of the neuropeptide oxytocin (OT) to modulate social and reproductive behavior, OT is likely involved in these cortical processes. However, little is known about the distribution of OT and OT receptors (OTR) within the neocortex. Using autoradiographic and neuroanatomical techniques, we characterized the cortical distribution of OT receptors (OTR) in prairie voles, a socially monogamous rodent species. We found that OTR density was low in the primary sensory areas (including primary somatosensory and auditory regions) but was quite high in association regions (including temporal and parietal association areas, and prelimbic regions). In the primary motor area as well as the temporal and parietal association areas, we observed differences in OTR density across cortical layers. Specifically, cortical layers 2/3 and 5 exhibited greater OTR density than layer 4. Our results point to a role for OT in integrating sensory and motor in the prairie vole brain, providing a complementary mechanism for the modulation of social interactions. Given the ability of early social experience and developmental manipulations of OT to affect the brain and behavior, these results suggest a novel mechanism for how OT may influence cortical organization.

Intranasal oxytocin (OT) affects a suite of human social behaviors, including trust, eye contact, and emotion recognition. However, it is unclear where oxytocin receptors (OXTR) and the structurally related vasopressin 1a receptors (AVPR1a) are expressed in the human brain. We have previously described a reliable, pharmacologically informed receptor autoradiography protocol for visualizing these receptors in postmortem primate brain tissue. We used this technique in human brainstem tissue to identify the neural targets of OT and vasopressin. To determine binding selectivity of the OXTR radioligand and AVPR1a radioligand, sections were incubated in four conditions: radioligand alone, radioligand with the selective AVPR1a competitor SR49059, and radioligand with a low or high concentration of the selective OXTR competitor ALS-II-69. We found selective OXTR binding in the spinal trigeminal nucleus, a conserved region of OXTR expression in all primate species investigated to date. We found selective AVPR1a binding in the nucleus prepositus, an area implicated in eye gaze stabilization. The tissue's postmortem interval (PMI) was not correlated with either the specific or nonspecific binding of either radioligand, indicating that it will not likely be a factor in similar postmortem studies. This study provides critical data for future studies of OXTR and AVPR1a in human brain tissue.

Oxytocin (OT) elicits weight loss in diet-induced obese (DIO) rodents, nonhuman primates, and humans, in part, by reducing food intake. Chronic OT administration produces more sustained weight loss in high-fat diet (HFD)-fed DIO rodents relative to chow-fed controls, but the reasons for this effect remain unclear. We hypothesized that HFD-induced obesity is associated with elevated OT receptor (OXTR) binding in brain regions where OT is known to cause decreased food intake and that this sensitized neural system is one mechanism by which OT preferentially elicits weight loss in DIO rodents. We therefore determined the impact of diet (HFD vs chow) and drug treatment (chronic OT infusion vs vehicle) on (1) OXTR binding in hindbrain and forebrain sites where OT suppresses food intake relative to control sites that express OXTR and (2) forebrain vasopressin 1a receptor (AVPR1a) density to evaluate the specificity of any OT effects. Using quantitative receptor autoradiography, we found that (1) diet composition failed to alter OXTR or AVPR1a binding; (2) chronic OT treatment produced largely global reductions in forebrain OXTR and AVPR1a binding without significantly altering hindbrain OXTR binding. These findings suggest that forebrain OXTR and AVPR1a are down-regulated in response to chronic OT treatment. Given that chronic intranasal OT may be used as a therapeutic strategy to treat obesity, future studies should consider the potential downregulatory effect that chronic treatment can have across forebrain and hindbrain nonapeptide receptors and assess the potential contribution of both receptor subtypes to the outcome measures.

Early experience and social context interact to alter the phenotype of complex social behaviors. These early experiences can also result in alterations to cortical organization and connections. Given the ability of the neuropeptide oxytocin (OT) to modulate social and reproductive behavior, OT is likely involved in these cortical processes. However, little is known about the distribution of OT and OT receptors (OTR) within the neocortex. Using autoradiographic and neuroanatomical techniques, we characterized the cortical distribution of OT receptors (OTR) in prairie voles, a socially monogamous rodent species. We found that OTR density was low in the primary sensory areas (including primary somatosensory and auditory regions) but was quite high in association regions (including temporal and parietal association areas, and prelimbic regions). In the primary motor area as well as the temporal and parietal association areas, we observed differences in OTR density across cortical layers. Specifically, cortical layers 2/3 and 5 exhibited greater OTR density than layer 4. Our results point to a role for OT in integrating sensory and motor in the prairie vole brain, providing a complementary mechanism for the modulation of social interactions. Given the ability of early social experience and developmental manipulations of OT to affect the brain and behavior, these results suggest a novel mechanism for how OT may influence cortical organization.

Paternal absence can significantly alter bio-behavioural development in many biparental species. This effect has generally been demonstrated by comparing the development of offspring reared under biparental care with those reared by a single mother. However, studies employing this design conflate two significant modifications to early-life experience: removal of father-specific qualities and the general reduction of offspring-directed care. In the socially monogamous prairie vole (Microtus ochrogaster), the experience of paternal absence without substitution during development inhibits partner preference formation in adulthood, a hallmark of social monogamy, in females and males. Employing alloparents as substitutes for fathers, our previous work demonstrated that paternal absence affects pair-bond formation in female offspring via reduced quantity of care, although it affects pair-bond formation in male offspring by means of a missing paternal quality (or qualities). Here, we present evidence that paternal absence (with and without alloparental substitution) may alter the ontogeny of neural oxytocin receptor (OXTR) and/or vasopressin 1a receptor (AVPR1a) distribution in male and female prairie voles. Compared to biparentally reared controls (BPC), male offspring reared in mother only (MON) and maternal-plus-alloparental (MPA) conditions show lower densities of OXTR in the central amygdala; and MPA males show lower densities of OXTR in the caudate putamen and nucleus accumbens. Early-life experience was not associated with differences in AVPR1a density in males. However, MON and MPA females show greater densities of AVPR1a in the medial amygdala than BPC; and MPA females show greater densities of AVPR1a in the ventromedial nucleus of the hypothalamus. We also demonstrate with corticosterone concentrations that MON and MPA offspring are not differentially susceptible to a stressor (ie, social isolation) than BPC offspring. These findings suggest that paternal absence, although likely not a salient early-life stressor, has neuroendocrine consequences for offspring, some of which may affect partner preference formation.

Developmental exposure to selective serotonin reuptake inhibitor (SSRI) increases the risk of Autism Spectrum Disorder (ASD), however, the underlying neurobiology of this effect is not fully understood. Here we used the socially monogamous prairie vole as a translational model of developmental SSRI exposure. Paired female prairie voles (n = 20) were treated with 5 mg/kg subcutaneous fluoxetine (FLX) or saline (SAL) daily from birth of the second litter until the day of birth of the 4th litter. This design created three cohorts of FLX exposure: postnatal exposure in litter 2, both prenatal and postnatal exposure in litter 3, and prenatal exposure in litter 4. Post-weaning, subjects underwent behavioral testing to detect changes in sociality, repetitive behavior, pair-bond formation, and anxiety-like behavior. Quantitative receptor autoradiography was performed for oxytocin, vasopressin 1a, and serotonin 1a receptor density in a subset of brains. We observed increased anxiety-like behavior and reduced sociality in developmentally FLX exposed adults. FLX exposure decreased oxytocin receptor binding in the nucleus accumbens core and central amygdala, and vasopressin 1a receptor binding in the medial amygdala. FLX exposure did not affect serotonin 1A receptor binding in any areas examined. Changes to oxytocin and vasopressin receptors may underlie the behavioral changes observed and have translational implications for the mechanism of the increased risk of ASD subsequent to prenatal SSRI exposure.

Pair bonding in humans and other socially monogamous species can have positive effects on health and well-being. These attachments also come with the potential for challenges such as separation, jealousy, or grief. Much of the work on the neurobiology of pair bonding in non-human primates has been carried out in coppery titi monkeys (Plecturocebus cupreus), a monogamous South American monkey, although these studies have been primarily in males. In the current study, we utilized female titi monkeys to experimentally examine responses to their monogamous male partner vs. a male stranger or being alone. Positron emission tomography (PET) scans were performed on eight adult female titi monkeys from well-established pairs. We used a within-subjects design in which each female underwent three different conditions after the fluorodeoxyglucose F18 (FDG) injection: a) the subject was reunited with her partner, b) encountered a stranger, or c) was alone in the experimental cage. Behavioural observations were recorded, and plasma assayed for cortisol. Females housed alone showed higher cortisol compared with either the partner or stranger conditions. FDG uptake was higher in the amygdala and hippocampus when interacting with the stranger than the partner. Proximity modulated the relationship between social condition and FDG uptake in several areas. Females entered into mutual proximity more frequently with the partner than with the stranger. Female titi monkeys have different physiological, neural, and behavioural reactions to being with their partner, a stranger male, or being alone.