Behavior In Prairie Voles Research Articles

Effects of short-term isolation on social behaviors in prairie voles.

Social isolation affects the brain and behavior in a variety of animals, including humans. Studies in traditional laboratory rodents, including mice and rats, have supported the idea that short-term social isolation promotes affiliative social behaviors, while long-term isolation promotes anti-social behaviors, including increased aggression. Whether the effects of isolation on the social behaviors of mice and rats generalize to other rodents remains understudied. In the current study, we characterized the effects of short-term (3-days) social isolation on the social behaviors of adult prairie voles (Microtus ochrogaster) during same-sex and opposite-sex social interactions. Our experiments revealed that short-term isolation did not affect rates of ultrasonic vocalizations or time spent in non-aggressive social behaviors and huddling during same-sex and opposite-sex interactions. Unexpectedly, although short-term isolation also did not affect time spent in resident-initiated and mutually-initiated aggressive behavior, we found that short-term isolation increased time spent in visitor-initiated aggression during male-male interactions. Our findings highlight the importance of comparative work across species and the consideration of social context to understand the diverse ways in which social isolation can impact social behavior.

Behavioral trajectories of aging prairie voles (Microtus ochrogaster): Adapting behavior to social context wanes with advanced age

Several studies using mice have examined the effects of aging on cognitive tasks, as well as sensory and motor functions. However, few studies have examined the influence of aging on social behavior. Prairie voles (Microtus ochrogaster) are a socially monogamous and biparental rodent that live in small family groups and are now among the most popular rodent models for studies examining social behavior. Although the social behavioral trajectories of early-life development in prairie voles have been well-studied, how social behavior may change throughout adulthood remains unknown. Here we examined behavior in virgin male and female prairie voles in four different age groups: postnatal day (PND) 60-80, 140-160, 220-240, and 300-320. All animals underwent testing in a novel object task, a dominance test, a resident-intruder test, and several iterations of social approach and social interaction tests with varying types of social stimuli (i.e., novel same-sex conspecific, novel opposite-sex conspecific, familiar same-sex sibling/cagemate, small group of novel same-sex conspecifics). We found that age influenced neophobia and dominance, but not social approach behavior. Further, we found that young adult, but not older adult, prairie voles adapt prosocial and aggressive behavior relative to social context, and that selective aggression occurs in relation to age even in the absence of a pair bond. Our results suggest that prairie voles calibrate social phenotype in a context-dependent manner in young adulthood and stop adjusting behavior to social context in advanced age, demonstrating that social behavior is plastic not only throughout early development, but also well into adulthood. Together, this study provides insight into age-related changes in social behavior in prairie voles and shows that prairie voles may be a viable model for studying the cognitive and physiological benefits of social relationships and social engagement in advanced age.

Transcriptomic analysis of paternal behaviors in prairie voles

BackgroundThe importance of fathers’ engagement in care and its critical role in the offspring’s cognitive and emotional development is now well established. Yet, little is known on the underlying neurobiology due to the lack of appropriate animal models. In the socially monogamous and bi-parental prairie vole (Microtus ochrogaster), while 60–80% of virgin males show spontaneous paternal behaviors (Paternal), others display pup-directed aggression (Attackers). Here we took advantage of this phenotypic dichotomy and used RNA-sequencing in three important brain areas to characterize gene expression associated with paternal behaviors of Paternal males and compare it to experienced Fathers and Mothers.ResultsWhile Paternal males displayed the same range and extent of paternal behaviors as experienced Fathers, we observed structure-specific transcriptomic differences between parental behaviors phenotypes. Using differential expression, gene set expression, as well as co-expression network analyses, we found that phenotypic differences between Paternal males and Attackers were mainly reflected by the lateral septum (LS), and to a lower extent, the nucleus accumbens (NAc), transcriptomes. In the medial preoptic area (MPOA), the profiles of gene expression mainly reflected differences between females and males regardless of their parental behaviors phenotype. Functional enrichment analyses of those gene sets associated with Paternal males or Attackers in the LS and the NAc revealed the involvement of processes related to the mitochondria, RNA translation, protein degradation processes, as well as epigenetic regulation of gene expression.ConclusionsBy leveraging the natural phenotypic differences in parental behaviors in virgin male prairie voles alongside fathers and mothers, we identified a marked structure- and phenotype-specific pattern of gene expression associated with spontaneous paternal behaviors independently from fatherhood and pair-bonding. The LS transcriptome related to the mitochondria, RNA translation, and protein degradation processes was thus highlighted as a primary candidate associated with the spontaneous display of paternal behaviors. Altogether, our observations further characterize the behavioral and transcriptomic signature of parental behaviors in the socially monogamous prairie vole and lay the groundwork to further our understanding of the molecular underpinnings of paternal behavior.

Amphetamine exposure alters behaviors, and neuronal and neurochemical activation in the brain of female prairie voles

Previous studies have shown that 3-day d-amphetamine (AMPH) treatment effectively induced conditioned place preferences (CPP) and impaired pair bonding behaviors in prairie voles (Microtus ochrogaster). Using this established animal model and treatment regimen, we examined the effects of the demonstrated threshold rewarding dose of AMPH on various behaviors and their potential underlying neurochemical systems in the brain of female prairie voles. Our data show that 3-day AMPH injections (0.2 mg/kg/day) impaired social recognition and decreased depressive-like behavior in females without affecting their locomotion and anxiety-like behaviors. AMPH treatment also decreased neuronal activation indicated by the labeling of the early growth response protein 1 (Egr-1) as well as the number of neurons double-labeled for Egr-1 and corticotrophin-releasing hormone (CRH) in the dentate gyrus (DG) of the hippocampus and paraventricular nucleus of the hypothalamus (PVN) in the brain. Further, AMPH treatment decreased the number of neurons double-labeled for Egr-1 and tyrosine hydroxylase (TH) but did not affect oxytocinergic neurons in the PVN or cell proliferation and neurogenesis markers in the DG. These data not only demonstrate potential roles of the brain CRH and dopamine systems in mediating disrupted social recognition and depressive-like behaviors by AMPH in female prairie voles, but also further confirm the utility of the prairie vole model for studying interactions between psychostimulants and social behaviors.

Individual and Combined Effects of Paternal Deprivation and Developmental Exposure to Firemaster 550 on Socio-Emotional Behavior in Prairie Voles.

The prevalence of neurodevelopmental disorders (NDDs) is rapidly rising, suggesting a confluence of environmental factors that are likely contributing, including developmental exposure to environmental contaminants. Unfortunately, chemical exposures and social stressors frequently occur simultaneously in many communities, yet very few studies have sought to establish the combined effects on neurodevelopment or behavior. Social deficits are common to many NDDs, and we and others have shown that exposure to the chemical flame retardant mixture, Firemaster 550 (FM 550), or paternal deprivation impairs social behavior and neural function. Here, we used a spontaneously prosocial animal model, the prairie vole (Microtus ochrogaster), to explore the effects of perinatal chemical (FM 550) exposure alone or in combination with an early life stressor (paternal absence) on prosocial behavior. Dams were exposed to vehicle (sesame oil) or 1000 µg FM 550 orally via food treats from conception through weaning and the paternal absence groups were generated by removing the sires the day after birth. Adult offspring of both sexes were then subjected to open-field, sociability, and a partner preference test. Paternal deprivation (PD)-related effects included increased anxiety, decreased sociability, and impaired pair-bonding in both sexes. FM 550 effects include heightened anxiety and partner preference in females but reduced partner preference in males. The combination of FM 550 exposure and PD did not exacerbate any behaviors in either sex except for distance traveled by females in the partner preference test and, to a lesser extent, time spent with, and the number of visits to the non-social stimulus by males in the sociability test. FM 550 ameliorated the impacts of parental deprivation on partner preference behaviors in both sexes. This study is significant because it provides evidence that chemical and social stressors can have unique behavioral effects that differ by sex but may not produce worse outcomes in combination.

Effects of developmental exposure to FireMaster® 550 (FM 550) on microglia density, reactivity and morphology in a prosocial animal model

Microglia are known to shape brain sex differences critical for social and reproductive behaviors. Chemical exposures can disrupt brain sexual differentiation but there is limited data regarding how they may impact microglia distribution and function. We focused on the prevalent flame retardant mixture Firemaster 550 (FM 550) which is used in foam-based furniture and infant products including strollers and nursing pillows because it disrupts sexually dimorphic behaviors. We hypothesized early life FM 550 exposure would disrupt microglial distribution and reactivity in brain regions known to be highly sexually dimorphic or associated with social disorders in humans. We used prairie voles (Microtus ochrogaster) because they display spontaneous prosocial behaviors not seen in rats or mice and are thus a powerful model for studying chemical exposure-related impacts on social behaviors and their underlying neural systems. We have previously demonstrated that perinatal FM 550 exposure sex-specifically impacts socioemotional behaviors in prairie voles. We first established that, unlike in rats, the postnatal colonization of the prairie vole brain is not sexually dimorphic. Vole dams were then exposed to FM 550 (0, 500, 1000, 2000 µg/day) via subcutaneous injections through gestation, and pups were directly exposed beginning the day after birth until weaning. Adult offspring’s brains were assessed for number and type (ramified, intermediate, ameboid) of microglia in the medial prefrontal cortex (mPFC), cerebellum (lobules VI-VII) and amygdala. Effects were sex- and dose-specific in the regions of interests. Overall, FM 550 exposure resulted in reduced numbers of microglia in most regions examined, with the 1000 µg FM 550 exposed males particularly affected. To further quantify differences in microglia morphology in the 1000 µg FM 550 group, Sholl and skeleton analysis were carried out on individual microglia. Microglia from control females had a more ramified phenotype compared to control males while 1000 µg FM 550-exposed males had decreased branching and ramification compared to same-sex controls. Future studies will examine the impact on the exposure to FM 550 on microglia during development given the critical role of these cells in shaping neural circuits.

Philip William Davidson, Ph.D. obituary

Microglia are known to shape brain sex differences critical for social and reproductive behaviors. Chemical exposures can disrupt brain sexual differentiation but there is limited data regarding how they may impact microglia distribution and function. We focused on the prevalent flame retardant mixture Firemaster 550 (FM 550) which is used in foam-based furniture and infant products including strollers and nursing pillows because it disrupts sexually dimorphic behaviors. We hypothesized early life FM 550 exposure would disrupt microglial distribution and reactivity in brain regions known to be highly sexually dimorphic or associated with social disorders in humans. We used prairie voles (Microtus ochrogaster) because they display spontaneous prosocial behaviors not seen in rats or mice and are thus a powerful model for studying chemical exposure-related impacts on social behaviors and their underlying neural systems. We have previously demonstrated that perinatal FM 550 exposure sex-specifically impacts socioemotional behaviors in prairie voles. We first established that, unlike in rats, the postnatal colonization of the prairie vole brain is not sexually dimorphic. Vole dams were then exposed to FM 550 (0, 500, 1000, 2000 µg/day) via subcutaneous injections through gestation, and pups were directly exposed beginning the day after birth until weaning. Adult offspring’s brains were assessed for number and type (ramified, intermediate, ameboid) of microglia in the medial prefrontal cortex (mPFC), cerebellum (lobules VI-VII) and amygdala. Effects were sex- and dose-specific in the regions of interests. Overall, FM 550 exposure resulted in reduced numbers of microglia in most regions examined, with the 1000 µg FM 550 exposed males particularly affected. To further quantify differences in microglia morphology in the 1000 µg FM 550 group, Sholl and skeleton analysis were carried out on individual microglia. Microglia from control females had a more ramified phenotype compared to control males while 1000 µg FM 550-exposed males had decreased branching and ramification compared to same-sex controls. Future studies will examine the impact on the exposure to FM 550 on microglia during development given the critical role of these cells in shaping neural circuits.

Social isolation and oxytocin antagonism increase emotion-related behaviors and heart rate in female prairie voles.

Social isolation influences depression- and anxiety-related disorders and cardiac function. Oxytocin may mediate these conditions through interactions with social behavior, emotion, and cardiovascular function, via central and/or peripheral mechanisms. The present study investigated the influence of oxytocin antagonism using L-368,899, a selective oxytocin receptor antagonist that crosses the blood-brain barrier, on depression- and anxiety-related behaviors and heart rate in prairie voles. This rodent species has translational value for investigating interactions of social stress, behavior, cardiac responses, and oxytocin function. Adult female prairie voles were socially isolated or co-housed with a sibling for 4weeks. A subset of animals in each housing condition was subjected to 4 sessions of acute L-368,899 (20mg/kg, ip) or saline administration followed by a depression- or anxiety-related behavioral assessment. A subset of co-housed animals was evaluated for cardiac function following acute administration of L-368,899 (20mg/kg, ip) and during behavioral assessments. Social isolation (vs. co-housing) increased depression- and anxiety-related behaviors. In isolated animals, L-368,899 (vs. vehicle) did not influence anxiety-related behaviors but exacerbated depression-related behaviors. In co-housed animals, L-368,899 exacerbated depression-related behaviors and increased heart rate at baseline and during behavioral tests. Social isolation produces emotion-related behaviors in prairie voles; central and/or peripheral oxytocin antagonism exacerbates these behavioral signs. Oxytocin antagonism induces depression-relevant behaviors and increases basal and stressor-reactive heart rate in co-housed prairie voles, similar to the consequences of social isolation demonstrated in this model. These results provide translational value for humans who experience behavioral and cardiac consequences of loneliness or social stress.

Helping behavior in prairie voles: A model of empathy and the importance of oxytocin

SummarySeveral studies suggest that rodents show empathic responses and helping behavior toward others. We examined whether prairie voles would help conspecifics who were soaked in water by opening a door to a safe area. Door-opening latency decreased as task sessions progressed. Female and male voles stayed close to the soaked voles' side at equal rates and opened the door with similar latencies. When the conspecific was not soaked in water, the door-opening latency did not decrease. This suggests that the distress of the conspecific is necessary for learning to open the door and that the door-opening performed by prairie voles corresponds to helping behavior. Additionally, we examined the helping behavior in prairie voles in which oxytocin receptors were genetically knocked out. Oxytocin receptor knockout voles demonstrated less learning of the door-opening behavior and less interest in soaked conspecifics. This suggests that oxytocin is important for the emergence of helping behavior.

Helping Behavior in Prairie Voles: A Model of Empathy and the Importance of Oxytocin

Several studies suggest that rodents show empathic responses and helping behavior toward others. We examined whether prairie voles (Microtus ochrogaster) would help conspecifics who were soaked in water by opening a door to a safe area. Door-opening latency decreased as task sessions progressed. When the conspecific was not soaked in water, the latency of the door-opening did not decrease, indicating that the distress of the conspecific is necessary for the learning of the door-opening. These suggest that prairie voles learn helping behavior. We found no sex difference in the door-opening latency or the interest in other voles soaked in water. Additionally, we also examined the helping behavior in prairie voles in which oxytocin receptors were genetically knocked out. Oxytocin receptor knockout voles demonstrated less learning of the door-opening and less interest in other voles soaked in water. This suggests that oxytocin is important for the emergence of helping behavior.

Effects of systemic endocannabinoid manipulation on social and exploratory behavior in prairie voles (Microtus ochrogaster).

Anandamide is an endocannabinoid that contributes to certain aspects of social behavior, like play and reward, by binding to cannabinoid receptor type 1 (CB1). Most interesting is the recent discovery that anandamide may be mobilized by oxytocin receptor activation under certain contexts, particularly in the nucleus accumbens. Given the established role of oxytocin and the nucleus accumbens in the neurobiology of pair-bonding, we investigated whether systemic administration of brain-permeable modulators of the endocannabinoid system could alter preferential partner contact in both male and female prairie voles. Specifically, we tested whether intraperitoneal administration of the neutral CB1 antagonist AM4113 (4.0-16.0mg/kg) or the anandamide hydrolysis inhibitor URB597 (5.0-20.0mg/kg) could prevent or facilitate partner preference formation, respectively. To further investigate the specificity of effects on partner preference, we repeated our URB597 dosing regimen on an additional group of females and tested their anxiety-related behavior in both an elevated-plus maze and a light/dark test. AM4113 administration had no effect on partner preference. But while URB597 also had no effect on partner preference, low-dose females did increase absolute preferential contact with either the partner or the stranger; individual females spent significant contact time with either the partner or the stranger. None of our outcome measures in either anxiety test showed significant effects of treatment. Our results reveal that experimentally increasing anandamide levels in female prairie voles can increase social contact with both a familiar and novel male via unknown mechanisms that are likely separate from anxiety reduction.

Investigation of Oxtr-expressing Neurons Projecting to Nucleus Accumbens using Oxtr-ires-Cre Knock-in prairie Voles (Microtus ochrogaster)

Social bonds such as parent–infant attachment or pair bonds can be critical for mental and physical well-being. The monogamous prairie vole (Microtus ochrogaster) has proven useful for examining the neural substrates regulating social behaviors, including social bonding. Oxytocin (OXT) and oxytocin receptor (OXTR) play critical roles in alloparental care, pair bonding and consoling behavior in prairie voles. While OXTR in a few regions, such as the nucleus accumbnes (NAcc), prefrontal cortex (PFC) and anterior cingulate cortex (ACC), have been implicated in regulating these behaviors, the extent to which other OXT sensitive areas modulate social behaviors has not been investigated. The NAcc is a central hub for modulating OXTR dependent social behaviors. To identify neurons expressing Oxtr in prairie vole brain, we generated gene knock-in voles expressing Cre recombinase in tandem with Oxtr (Oxtr-ires-Cre) using CRISPR/Cas9 genome editing. We confirmed Oxtr and Cre mRNA co-localization in NAcc, validating this model. Next, we identified putative Oxtr-expressing neurons projecting to NAcc by infusing retrograde CRE-dependent EGFP AAV into NAcc and visualizing fluorescence. We found enhanced green fluorescent protein (EGFP) positive neurons in anterior olfactory nucleus, PFC, ACC, insular cortex (IC), paraventricular thalamus (PVT), basolateral amygdala (BLA), and posteromedial and posterolateral cortical amygdaloid area (PMCo, PLCo). The ACC to NAcc OXTR projection may represent a species-specific circuit since Oxtr-expressing neurons in the ACC of mice were reported not to project to the NAcc. This is the first delineation of Oxtr-expressing neural circuits in the prairie vole, and demonstrates the utility of this novel genetically modified organism for characterizing OXTR circuits involved in social behaviors.

Paternal deprivation impairs social behavior putatively via epigenetic modification to lateral septum vasopressin receptor.

Although it is well appreciated that the early-life social environment asserts subsequent long-term consequences on offspring brain and behavior, the specific mechanisms that account for this relationship remain poorly understood. Using a novel assay that forced biparental pairs or single mothers to prioritize caring for offspring or themselves, we investigated the impact of parental variation on adult expression of nonapeptide-modulated behaviors in prairie voles. We demonstrated that single mothers compensate for the lack of a co-parent. Moreover, mothers choose to invest in offspring over themselves when faced with a tradeoff, whereas fathers choose to invest in themselves. Furthermore, our study suggests a pathway whereby variation in parental behavior (specifically paternal care) may lead to alterations in DNA methylation within the vasopressin receptor 1a gene and gene expression in the lateral septum. These differences are concomitant with changes in social approach, a behavior closely associated with septal vasopressin receptor function.

Mechanisms of Convergent Egg Provisioning in Poison Frogs.

Parental provisioning of offspring with physiological products (nursing) occurs in many animals, yet little is known about the neuroendocrine basis of nursing in non-mammalian species. Within amphibians, maternal provisioning has evolved multiple times, with mothers of some species feeding unfertilized eggs to their developing offspring until tadpoles complete metamorphosis [1-3]. We conducted field studies in Ecuador and Madagascar to ask whether convergence at the behavioral level provides similar benefits to offspring and relies on shared neural mechanisms in dendrobatid and mantellid poison frogs. At an ecological level, we found that nursing allows poison frogs to provide chemical defenses to their tadpoles in both species. At the neural level, nursing was associated with increased activity in the lateral septum and preoptic area, demonstrating recruitment of shared brain regions in the convergent evolution of nursing within frogs and across vertebrates [4]. In contrast, only mantellids showed increased oxytocin neuron activity akin to that in nursing mammals [5], suggesting evolutionary versatility in molecular mechanisms. Our findings demonstrate that maternal provisioning provides similar potential benefits to offspring and relies on similar brain regions in poison frog species with convergently evolved toxicity and maternal care. VIDEO ABSTRACT.

Sex-specific effects of perinatal FireMaster® 550 (FM 550) exposure on socioemotional behavior in prairie voles

The rapidly rising incidence of neurodevelopmental disorders with social deficits is raising concern that developmental exposure to environmental contaminants may be contributory. Firemaster 550 (FM 550) is one of the most prevalent flame-retardant (FR) mixtures used in foam-based furniture and baby products and contains both brominated and organophosphate components. We and others have published evidence of developmental neurotoxicity and sex specific effects of FM 550 on anxiety-like and exploratory behaviors. Using a prosocial animal model, we investigated the impact of perinatal FM 550 exposure on a range of socioemotional behaviors including anxiety, attachment, and memory. Virtually unknown to toxicologists, but widely used in the behavioral neurosciences, the prairie vole (Microtus ochrogaster) is a uniquely valuable model organism for examining environmental factors on sociality because this species is spontaneously prosocial, biparental, and displays attachment behaviors including pair bonding. Dams were exposed to 0, 500, 1000, or 2000 μg of FM 550 via subcutaneous (sc) injections throughout gestation, and pups were directly exposed beginning the day after birth until weaning. Adult offspring of both sexes were then subjected to multiple tasks including open field, novel object recognition, and partner preference. Effects were dose responsive and sex-specific, with females more greatly affected. Exposure-related outcomes in females included elevated anxiety, decreased social interaction, decreased exploratory motivation, and aversion to novelty. Exposed males also had social deficits, with males in all three dose groups failing to show a partner preference. Our studies demonstrate the utility of the prairie vole for investigating the impact of chemical exposures on social behavior and support the hypothesis that developmental FR exposure impacts the social brain. Future studies will probe the possible mechanisms by which these effects arise.

Early developmental exposure to inorganic mercury does not alter affiliative behavior of adult prairie voles (Microtus ochrogaster)

Mercury chloride exposure through drinking water in adult male prairie voles (Microtus ochrogaster) has been shown to alter their social behavior. Here, we examined the potential disruption of adult social behavior in prairie voles that were exposed to 60 ppm mercury during early development. We used a cross-fostering approach to test the effects of mercury exposure: (1) from conception until birth; (ii) from birth until weaning; and (iii) from conception until weaning, on adult affiliative behavior. Untreated and mercury-treated voles were given the option of remaining in an empty cage or affiliating with a same-sex conspecific in a 3-h choice test. We found that early developmental mercury exposure had little if any effect on the reproductive success of breeder pairs or on affiliative behavior by either sex when subjects were tested as adults. These results suggest that, at least in the context of the behavior tested, the effects of early developmental exposure to mercury do not permanently alter adult prairie vole affiliative behavior, or do so in a way that is too subtle to be detected using the current testing paradigm.

Differences in Neural Response to Romantic Stimuli in Monogamous and Non-Monogamous Men.

In non-human animal research, studies comparing socially monogamous and promiscuous species of voles (Microtus) have identified some key neural differences related to monogamy and non-monogamy. Specifically, densities of the vasopressin V1a receptor and dopamine D2 receptors in subcortical reward-related and limbic areas of the brain have been linked to monogamous behavior in prairie voles (Microtus ochrogaster). Similar brain areas have been shown to be correlated with feelings of romantic love in monogamously pair-bonded humans. Humans vary in the degree to which they engage in (non-)monogamous behaviors. The present study examined the differences in neural activation in response to sexual and romantic stimuli in monogamous (n=10) and non-monogamous (n=10) men. Results indicated that monogamous men showed more reward-related neural activity when viewing romantic pictures compared to non-monogamous men. Areas with increased activation for monogamous men were all in the right hemisphere and included the thalamus, accumbens, striatum, pallidum, insula, and orbitofrontal cortex. There were no significant differences between groups in activation to sexual stimuli. These results demonstrate that the neural processing of romantic images is different for monogamous and non-monogamous men. There is some overlap in the neural areas showing increased activation in monogamous men in the present study and the neural areas that show differences in the vole models of monogamy and affiliation. Future research will be needed to clarify whether similar factors are contributing to the neural differences seen in monogamous and non-monogamous humans and voles.

Exploration in a dispersal task: Effects of early experience and correlation with other behaviors in prairie voles (Microtus ochrogaster)

Socially monogamous prairie voles (Microtus ochrogaster) display remarkable individual variation in social behaviors, which has been associated with differences in early life experience and neuropeptide receptor densities. These differences are also seen in the wild, where approximately 70% of young voles remain in their natal group as non-breeding alloparents, while the other 30% disperse. We investigated whether natural variation in early parental care could contribute to offspring’s willingness to “disperse” (willingness to explore) in a laboratory context. Behavioral differences between dispersers and residents could also provide a way to interpret individual variation in other behaviors commonly observed under laboratory conditions. Breeder pairs ranked as high, medium or low-contact, according to the amount of early parental care they provided to offspring, were used to produce and rear experimental subjects. Effects of early parental care on the offspring’s willingness to disperse were seen at post-natal day 21, with high-contact offspring spending more time in the start cage and low-contact offspring spending more time exploring. Variations in parental care were also associated with differences in juvenile and adult behaviors that could potentially encourage philopatry or dispersal behavior in the wild. High-contact offspring displayed less anxiety-like behavior compared to low-contact animals. Low-contact offspring displayed the lowest amount of alloparental care. High-contact offspring spent more time in side-by-side contact with a potential partner compared to medium and low-contact offspring. These results suggest that variations in early parental care can impact weanlings’ exploratory behavior, but that philopatry is not driven by high anxiety.

Oxytocin, social cognition and psychiatry.

Oxytocin (OT) has an ancient role in modulating sensing and responding to social stimuli, from nematodes to man. OT regulates not only mammalian labor and nursing, but also maternal behavior. There is increasing evidence that OT influences human parenting and mediates the impact of parenting on infant socio-emotional development (Rilling and Young, 2014). Preclinical studies suggest that OT increases the salience and rewarding value of social stimuli. OT acts in the rodent amygdala to enhance the salience of social olfactory cues. thereby facilitating social recognition, in the striatum to mediate social reward and in the hippocampus to enhance signal to noise neurotransmission. These fundamental processes likely contribute to more complex OT-mediated behaviors, including social bonding. The effects of OT on social information processing in rodents make it an enticing pharmacological target for enhancing social cognition. However, two issues introduce skepticism for translating the compelling preclinical observations into effective pharmacotherapies to improve social functioning in psychiatric disorders, including autism and schizophrenia: (1) rodents use olfaction as the primary social perception modality, while primates rely more on visual and auditory social perception; (2) little is known regarding the pharmacokinetics of current OT administration methods or the impact of chronic OT treatment. Recent studies from our laboratory address these issues. A common polymorphism in the human OT receptor (OXTR) gene predicts face recognition skills in families with a child with autism. This effect was present in all family members in two independent populations, yet there was no evidence of an association with autism diagnosis (Skuse et al, 2014). This study supports a role for the OT system in human visual social information processing analogous to its role in olfactory processing in rodents. Nonhuman primates are useful for exploring the mechanisms of intranasal OT (IN-OT) administration. We showed that OT administered nasally by a pediatric nebulizer modestly elevates OT in the cerebrospinal fluid of anesthetized macaques (Modi et al, 2014). Importantly, intranasal OT also robustly elevated plasma OT for an extended period of time. Thus IN-OT may increase brain OT signaling, but peripheral mechanisms should be considered. Comparative studies of brain OXTR distribution in primates reveal the potential mechanisms by which OT modulates social information processing (Freeman et al, 2014a, 2014b). In all primate species examined, OXTRs are concentrated in cholinergic regions involved in visual and auditory processing, including the nucleus basalis of Meynert, which coordinates neural activity in the amygdala and cortex, thereby modulating attention to visual cues. IN-OT may enhance some aspects of social cognition through the mechanisms described above, but the efficacy may be limited by brain penetration. Stimulating endogenous central OT release pharmacologically is a viable alternative for increasing OT neural signaling. Melanocortin receptor agonists stimulate OT release from hypothalamic slices, potentiate OT release in the ventral striatum, and enhance OT-dependent behavior in prairie voles (unpublished data). Neonatal melanocortin receptor activation acutely activates OT neurons, and daily treatment for the first week of life enhances adult social bonding in prairie voles (Barrett et al, 2014). Thus, the OT system remains an attractive target for clinically enhancing social cognition, and alternative pharmacological strategies for enhancing OT neurotransmission should be explored.

Social partners prevent alcohol relapse behavior in prairie voles

There is robust evidence for a protective role of interpersonal factors such as social support on alcohol relapse, but research on the mechanisms that social factors may be acting on to effectively protect individuals against relapse is lacking. Prairie voles are highly social, monogamous rodents that freely self-administer ethanol in high amounts, and are a useful model for understanding social influences on alcohol drinking. Here we investigated whether prairie voles can be used to model social influences on relapse using the alcohol deprivation effect, in which animals show a transient increase in ethanol drinking following deprivation. In Experiment I, subjects were housed alone during four weeks of 24-h access to 10% ethanol in a two-bottle choice test. Ethanol was then removed from the cage for 72 h. Animals remained in isolation or were then housed with a familiar same-sex social partner, and ethanol access was resumed. Animals that remained isolated showed an increase in ethanol intake relative to pre-deprivation baseline, indicative of relapse-like behavior. However, animals that were socially housed did not show an increase in ethanol intake, and this was independent of whether the social partner also had access to ethanol. Experiment II replicated the alcohol deprivation effect in a separate cohort of isolated animals. These findings demonstrate that prairie voles display an alcohol deprivation effect and suggest a 'social buffering' effect of relapse-like behavior in the prairie vole. This behavioral paradigm provides a novel approach for investigating the behavioral and neurobiological underpinnings of social influences on alcohol relapse.