Prairie Voles Research Articles

Mating and social exposure induces an opioid-dependent conditioned place preference in male but not in female prairie voles (Microtus ochrogaster)

In rodents, sexual stimulation induces a positive affective state that is evaluated by the conditioned place preference (CPP) test. Opioids are released during sexual behavior and modulate the rewarding properties of this behavior. Prairie voles (Microtus ochrogaster) are a socially monogamous species, in which copulation with cohabitation for 6h induces a pair bond. However, the mating-induced reward state that could contribute to the establishment of the long-term pair bond has not been evaluated in this species. The present study aimed to determine whether one ejaculation or cohabitation with mating for 6h is rewarding for voles. We also evaluated whether this state is opioid dependent. Our results demonstrate that mating with one ejaculation and social cohabitation with mating for 6h induce a CPP in males, while exposure to a sexually receptive female without mating did not induce CPP. In the female vole, mating until one ejaculation, social cohabitation with mating, or exposure to a male without physical interaction for 6h did not induce CPP. To evaluate whether the rewarding state in males is opioid dependent, the antagonist naloxone was injected i.p. The administration of naloxone blocked the rewarding state induced by one ejaculation and by social cohabitation with mating. Our results demonstrate that in the prairie vole, on the basis of the CPP in the testing conditions used here, the stimulation received with one ejaculation and the mating conditions that lead to pair bonding formation may be rewarding for males, and this reward state is opioid dependent.

Prairie vole pairs split up if only one is a heavy drinker

Prairie vole pairs split up if only one is a heavy drinker

Vasopressinergic Neurocircuitry Regulating Social Attachment in a Monogamous Species.

The prairie vole (Microtus ochrogaster) is a socially monogamous rodent species that forms a lasting connection between mates, known as a pair bond. The pair bond is primarily characterized by three distinct behaviors: partner preference, selective aggression, and biparental care of the young. The presence of these behaviors in the prairie vole and their absence in closely related non-monogamous species makes the prairie vole an important model of social relationships and facilitates the study of the neurobiological mechanisms of social affiliation and attachment. The nona-peptide arginine-vasopressin (AVP) is an important neuromodulator of social behavior and has been implicated in the regulation of the pair bond-related behaviors of the prairie vole, through activation of the AVP receptor subtype 1a (AVPR1a). Modulation of AVPR1a activity in different regions of the prairie vole brain impacts pair bond behavior, suggesting a role of AVP in neurocircuitry responsible for the regulation of social attachment. This review will discuss findings that have suggested the role of AVP in regulation of the pair bond-related behaviors of the prairie vole and the specific brain regions through which AVP acts to impact these unique behaviors.

Individual Differences in Social Behavior and Cortical Vasopressin Receptor: Genetics, Epigenetics, and Evolution.

Social behavior is among the most complex and variable of traits. Despite its diversity, we know little about how genetic and developmental factors interact to shape natural variation in social behavior. This review surveys recent work on individual differences in the expression of the vasopressin 1a receptor (V1aR), a major regulator of social behavior, in the neocortex of the socially monogamous prairie vole. V1aR exhibits profound variation in the retrosplenial cortex (RSC), a region critical to spatial and contextual memory. RSC-V1aR abundance is associated with patterns of male space-use and sexual fidelity in the field: males with high RSC-V1aR show high spatial and sexual fidelity to partners, while low RSC-V1aR males are significantly more likely to mate outside the pair-bond. Individual differences in RSC-V1aR are predicted by a set of linked single nucleotide polymorphisms within the avpr1a locus. These alternative alleles have been actively maintained by selection, suggesting that the brain differences represent a balanced polymorphism. Lastly, the alleles occur within regulatory sequences, and result in differential sensitivity to environmental perturbation. Together the data provide insight into how genetic, epigenetic and evolutionary forces interact to shape the social brain.

Cardiovascular control is associated with pair-bond success in male prairie voles.

Social support structures reduce mortality and morbidity in humans, but the mechanisms underlying these reductions are not fully understood. The prevailing hypothesis is that social support buffers stress and reduces allostatic load, thereby increasing longevity. However, the possibility that affiliative social interactions confer health benefits independent of stress buffering is understudied. We examined autonomic function in prairie voles - arguably the premier species for modeling human social affiliation - to assess the possibility that the formation of strong social bonds alters autonomic function and contributes to health benefits. We examined cardiovascular measures in male prairie voles before and after two weeks of cohabitation with a female, during a partner preference test, and during social isolation. There were strong correlations between social contact and heart rate (HR) and heart rate variability (HRV), the latter being an index of autonomic nervous system function. Males that successfully pair-bonded with their partners displayed higher HRV prior to pairing than did unsuccessful males, suggesting higher basal parasympathetic tone in the successful males. HRV increased further still when pair-bonded males huddled quietly with their mates during the partner preference test. Non-pair-bonded males not only had lower baseline parasympathetic activity, but showed a further decrease after pairing. HR increased and HRV decreased during social isolation only in pair-bonded males. Since differences in HRV are thought to reflect the relative influences of the parasympathetic and sympathetic nervous systems on cardiac function, these results suggest that autonomic balance may contribute to social bonding and thus to its health benefits.

Effects of pair bonding on parental behavior and dopamine activity in the nucleus accumbens in male prairie voles.

Male parental care is a vital behavior for the development as well as the physical and mental well-being of the young. However, little is known about the neurochemical regulation of male parental behavior, mainly due to the lack of appropriate animal models. In this study, we used the socially monogamous male prairie vole (Microtus ochrogaster) to investigate the effect of pair-bonding experience on paternal behavior and dopamine (DA) signaling in the nucleus accumbens (NAcc) in the brain. We compared sexually naïve males with males that were pair bonded with a female for two weeks. Our data showed that pair-bonded males displayed enhanced paternal behavior, particularly in pup licking/grooming, associated with increased DA type-1 receptor (D1R) protein expression in the NAcc, compared to sexually naïve males. Site-specific brain microdialysis revealed a significant, but transient, increase in DA release in the NAcc associated with pup exposure in both groups of the males. Further, pharmacological blockade of D1R in the NAcc decreased pup licking/grooming in the pair-bonded males. Together, our data demonstrate that pair-bonding experience with a female facilitated male parental behavior via NAcc D1R mediation in male prairie voles.

Effects of methamphetamine on alloparental behavior in male and female prairie voles

Psychostimulant abuse is associated with a variety of impairments in social functioning, including an increased frequency of depression and aggression and deficits in social cognition. Psychostimulants reduce social investigation in rats and mice; however, it is less clear how other forms of social behavior (e.g., prosocial behavior) are affected. Females are also generally more sensitive to the effects of psychostimulants on locomotion and stereotyped behavior, which suggests that females might also display greater disruption of prosocial behavior. In order to test the hypothesis that psychostimulants reduce prosocial behavior and that females are more vulnerable, we treated adult male and female prairie voles with methamphetamine for three days (0, 0.2 or 2.0mg/kg, i.p.) and examined effects on locomotion and alloparental behavior. The lower methamphetamine dose increased activity in the open field in males and reduced locomotion in females. Methamphetamine-treated males took longer to enter the pup chamber, but both sexes displayed reduced pup contact following treatment with the lower methamphetamine dose. The methamphetamine-induced reduction in prosocial behavior was not associated with changes in pup-directed aggression in males or females. In order to investigate potential mechanisms underlying these changes in behavior, we measured adrenal weights as a proxy for activation of the hypothalamic-pituitary-adrenal (HPA) axis. The higher methamphetamine dose increased adrenal weights. Collectively, these data demonstrate that methamphetamine administration reduces alloparental behavior in both sexes and that females are more sensitive to some of the effects of this drug (e.g., locomotion/stereotyped behavior and possibly stimulation of the HPA axis).

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.

Oxytocin Neurons Exhibit Extensive Functional Plasticity Due To Offspring Age in Mothers and Fathers.

The needs of offspring change as they develop. Thus, parents should concomitantly change their investment based on the age-related needs of the offspring as they mature. Due to the high costs of parental care, it is optimal for parents to exhibit a shift from intense caregiving of young offspring to promoting independence in older offspring. Yet, the neural mechanisms that underlie shifts in parental behavior are poorly understood, and little is known about how the parental brain responds to offspring of different ages. To elucidate mechanisms that relate to shifts in parental behavior as offspring develop, we examined behavioral and neural responses of male and female prairie voles (Microtus ochrogaster), a biparental rodent, to interactions with offspring at different stages of development (ranging from neonatal to weaning age). Importantly, in biparental species, males and females may adjust their behavior differentially as offspring develop. Because the nonapeptides, vasopressin (VP) and oxytocin (OT), are well known for modulating aspects of parental care, we focused on functional activity of distinct VP and OT cell groups within the maternal and paternal brain in response to separation from, reunion (after a brief period of separation) with, or no separation from offspring of different ages. We found several differences in the neural responses of individual VP and OT cell groups that varied based on the age of pups and sex of the parent. Hypothalamic VP neurons exhibit similar functional responses in both mothers and fathers. However, hypothalamic and amygdalar OT neurons exhibit differential functional responses to being separated from pups based on the sex of the parent. Our results also reveal that the developmental stage of offspring significantly impacts neural function within OT, but not VP, cell groups of both mothers and fathers. These findings provide insight into the functional plastic capabilities of the nonapeptide system, specifically in relation to parental behavior. Identifying neural mechanisms that exhibit functional plasticity can elucidate one way in which animals are able to shift behavior on relatively short timescales in order to exhibit the most context-appropriate and adaptive behaviors.

Cryptic sexual dimorphism in spatial memory and hippocampal oxytocin receptors in prairie voles (Microtus ochrogaster)

Sex differences are well documented and are conventionally associated with intense sex-specific selection. For example, spatial memory is frequently better in males, presumably due to males' tendency to navigate large spaces to find mates. Alternatively, monogamy (in which sex-specific selection is relatively relaxed) should diminish or eliminate differences in spatial ability and the mechanisms associated with this behavior. Nevertheless, phenotypic differences between monogamous males and females persist, sometimes cryptically. We hypothesize that sex-specific cognitive demands are present in monogamous species that will influence neural and behavioral phenotypes. The effects of these demands should be observable in spatial learning performance and neural structures associated with spatial learning and memory. We analyzed spatial memory performance, hippocampal volume and cell density, and hippocampal oxytocin receptor (OTR) expression in the socially monogamous prairie vole. Compared to females, males performed better in a spatial memory and spatial learning test. Although we found no sex difference in hippocampal volume or cell density, male OTR density was significantly lower than females, suggesting that performance may be regulated by sub-cellular mechanisms within the hippocampus that are less obvious than classic neuroanatomical features. Our results suggest an expanded role for oxytocin beyond facilitating social interactions, which may function in part to integrate social and spatial information.

Voluntary physical exercise protects against behavioral and endocrine reactivity to social and environmental stressors in the prairie vole

ABSTRACTPhysical activity can combat detrimental effects of stress. The current study examined the potential protective effects of exercise against a combination of social isolation and chronic mild stress (CMS) in a prairie vole model. Female voles were isolated for 4 weeks, with the addition of CMS during the final 2 weeks. Half of the voles were allowed access to a running wheel during this final 2 weeks, while the other half remained sedentary. Animals underwent behavioral tests to assess depressive- and anxiety-behaviors. In a subset of animals, plasma was collected 10 minutes after behavioral testing for corticosterone analysis. In a separate subset, brains were collected 2 hours after behavioral testing for cFos analysis in the paraventricular nucleus (PVN). Voles in the exercise group displayed significantly lower depressive- and anxiety-behaviors, and displayed significantly lower corticosterone levels, compared to animals in the sedentary group. There was no difference in PVN cFos activity between groups. Interestingly, animals that moderately exercised displayed lower levels of depressive-behavior and attenuated corticosterone reactivity compared to animals in the low and high activity subgroups. These findings suggest that physical activity can protect against a combination of social and environmental stressors.

Development of a radioligand for imaging V1a vasopressin receptors with PET

A series of vasopressin receptor V1a ligands have been synthesized for positron emission tomography (PET) imaging. The lead compound (1S,5R)-1 ((4-(1H-indol-3-yl)-3-methoxyphenyl) ((1S,5R)-1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-yl)methanone) and its F-ethyl analog 6c exhibited the best combination of high binding affinity and optimal lipophilicity within the series. (1S,5R)-1 was radiolabeled with 11C for PET studies. [11CH3](1S,5R)-1 readily entered the mouse (4.7% ID/g tissue) and prairie vole brains (∼2% ID/g tissue) and specifically (30–34%) labeled V1a receptor. The common animal anesthetic Propofol significantly blocked the brain uptake of [11CH3](1S,5R)-1 in the mouse brain, whereas anesthetics Ketamine and Saffan increased the uptake variability. Future PET imaging studies with V1a radiotracers in non-human primates should be performed in awake animals or using anesthetics that do not affect the V1a receptor.

Effects of avpr1a length polymorphism on male social behavior and reproduction in semi‐natural populations of prairie voles (Microtus ochrogaster)

AbstractIntraspecific variation in sociosexual behavior has typically been investigated in the context of its relationship with environmental factors, but neurogenetic factors can also influence sociosexual behavior. In laboratory studies of prairie voles (Microtus ochrogaster), length polymorphism of microsatellite DNA within the gene (avpr1a) encoding the vasopressin 1a receptor is correlated with variation in male sociosexual behavior. However, field studies of prairie voles have found the relationship between male avpr1a microsatellite allele length and sociosexual behavior to be more ambiguous, possibly because most males had alleles of intermediate length. We tested the hypothesis that avpr1a microsatellite allele length mediates male sociosexual behavior in field settings by releasing voles into field enclosures where every male possessed two avpr1a microsatellite alleles at least one standard error longer or shorter than the mean length in their population of origin. Voles from an Illinois and Kansas population were examined separately as social monogamy appears more prevalent in the Illinois population. Illinois males with long avpr1a microsatellite alleles had smaller home ranges and overlapped a greater proportion of the home range of the female that they overlapped the most. Kansas males showed the opposite pattern. Illinois, but not Kansas, males with long avpr1a microsatellite alleles sired offspring with more females and sired more litters. Our results support the hypothesis that genetic variation associated with the avpr1a gene plays a role in mediating male prairie vole sociosexual behavior in nature. However, the relationship between specific male behaviors and male avpr1a microsatellite allele length sometimes differed significantly between Kansas and Illinois voles, suggesting relationships between specific male sociosexual behaviors and polymorphism associated with the avpr1a locus are complex, possibly involving specific nucleotide sequences or other population‐specific genetic differences.

Alcohol Consumption Decreases Oxytocin Neurons in the Anterior Paraventricular Nucleus of the Hypothalamus in Prairie Voles.

Alcohol use disorders are associated with dysfunctional social relationships and stress responses. The neuropeptides oxytocin (OT) and vasopressin (AVP) are known to orchestrate or mediate many aspects of social behavior, stress responses, and ingestive behaviors. Because of the overlap between the effects of alcohol and the roles of OT and AVP, we sought to determine whether alcohol consumption altered expression of OT and AVP in the paraventricular nucleus (PVN) of the hypothalamus, one of the key sites for OT and AVP synthesis. Pair-housed adult male prairie voles were allowed to consume 15% ethanol versus water in the home cage continuously (Continuous-Access [CA] group) or every other day for 4hours (Intermittent-Access [IA] group). Control animals never had access to alcohol. After 7weeks, animals were sacrificed and their brains were removed and immunohistochemical analysis of OT- and AVP-immunopositive neurons was performed. OT-immunopositive neurons were significantly decreased in the anterior PVN in the CA but not IA group, relative to Control animals, suggesting that continuous alcohol consumption decreases the number of OT neurons. There was no effect of alcohol consumption on posterior PVN OT neurons, and no effect on PVN AVP neurons. These data show that continuous-access voluntary alcohol consumption is associated with decreased OT neurons in the anterior PVN, suggesting that alcohol-induced alterations in the OT system should be investigated as a mechanism for alcohol-related changes in social behavior, stress responses, and exacerbation of alcohol use disorders.

Oxytocin reduces alcohol consumption in prairie voles

Alcohol use disorder (AUD) negatively affects millions of people every year in the United States, and effective treatments for AUD are still needed. The neuropeptide oxytocin has shown promise for reducing alcohol drinking in mice and rats. Because oxytocin also plays a key role in complex prosocial behaviors like bonding and attachment, we tested the effect of oxytocin on alcohol drinking in prairie voles, a species that both consumes high amounts of alcohol and forms oxytocin dependent social bonds in a manner similar to humans. Oxytocin treatment (1.0, 3.0, and 10.0mg/kg, i.p.) reduced alcohol consumption in male and female prairie voles in animals that had access to 15% ethanol vs water every other day for 12 alcohol drinking sessions. In animals with continuous access to 15% alcohol and water, oxytocin (3.0mg/kg) reduced alcohol consumption only in the first hour of access after treatment, with no significant effects on consumption over the 24-hr period. In an open field locomotor test, oxytocin (1.0, 3.0, and 10.0mg/kg, i.p.) did not affect overall locomotor activity; however, ethanol (2g/kg, i.p.) increased locomotor activity in males and females, and produced anxiolytic effects (increased time in the center of an open field) in females only. Because prairie voles have been shown to match the alcohol consumption of their cage mate, we evaluated the relationship between cage mates' alcohol drinking. There was an overall pattern of social facilitation (consumption by one cage mate predicted consumption by the other cage mate); however, we found significant individual differences across cages in which many cages did not show significant matching, and, in some cases one cage mate's consumption negatively predicted the other cage mate's consumption. Overall, our data provide support for the potential of oxytocin as a treatment to reduce alcohol consumption.

Pairing Increases Activation of V1aR, but not OTR, in Auditory Regions of Zebra Finches: The Importance of Signal Modality in Nonapeptide-Social Behavior Relationships.

Social relationships are complex, involving the production and comprehension of signals, individual recognition, and close coordination of behavior between two or more individuals. The nonapeptides oxytocin and vasopressin are widely believed to regulate social relationships. These findings come largely from prairie voles, in which nonapeptide receptors in olfactory neural circuits drive pair bonding. This research is assumed to apply to all species. Previous reviews have offered two competing hypotheses. The work of Sarah Newman has implicated a common neural network across species, the Social Behavior Network. In contrast, others have suggested that there are signal modality-specific networks that regulate social behavior. Our research focuses on evaluating these two competing hypotheses in the zebra finch, a species that relies heavily on vocal/auditory signals for communication, specifically the neural circuits underlying singing in males and song perception in females. We have demonstrated that the quality of vocal interactions is highly important for the formation of long-term monogamous bonds in zebra finches. Qualitative evidence at first suggests that nonapeptide receptor distributions are very different between monogamous rodents (olfactory species) and monogamous birds (vocal/auditory species). However, we have demonstrated that social bonding behaviors are not only correlated with activation of nonapeptide receptors in vocal and auditory circuits, but also involve regions of the common Social Behavior Network. Here, we show increased Vasopressin 1a receptor, but not oxytocin receptor, activation in two auditory regions following formation of a pair bond. To our knowledge, this is the first study to suggest a role of nonapeptides in the auditory circuit in pair bonding. Thus, we highlight converging mechanisms of social relationships and also point to the importance of studying multiple species to understand mechanisms of behavior.

Genetic variation in the developmental regulation of cortical avpr1a among prairie voles.

Early experiences can have enduring impacts on brain and behavior, but the strength of these effects can be influenced by genetic variation. In principle, polymorphic CpGs (polyCpGs) may contribute to gene-by-environment interactions (G × E) by altering DNA methylation. In this study, we investigate the influence of polyCpGs on the development of vasopressin receptor 1a abundance in the retrosplenial cortex (RSC-V1aR) of prairie voles (Microtus ochrogaster). Two alternative alleles ('HI'/'LO') predict RSC avpr1a expression, V1aR abundance and sexual fidelity in adulthood; these alleles differ in the frequency of CpG sites and in methylation at a putative intron enhancer. We hypothesized that the elevated CpG abundance in the LO allele would make homozygous LO/LO voles more sensitive to developmental perturbations. We found that genotype differences in RSC-V1aR abundance emerged early in ontogeny and were accompanied by differences in methylation of the putative enhancer. As predicted, postnatal treatment with an oxytocin receptor antagonist (OTA) reduced RSC-V1aR abundance in LO/LO adults but not their HI/HI siblings. Similarly, methylation inhibition by zebularine increased RSC-V1aR in LO/LO adults, but not in HI/HI siblings. These data show a gene-by-environment interaction in RSC-V1aR. Surprisingly, however, neither OTA nor zebularine altered adult methylation of the intronic enhancer, suggesting that differences in sensitivity could not be explained by CpG density at the enhancer alone. Methylated DNA immunoprecipiation-sequencing showed additional differentially methylated regions between HI/HI and LO/LO voles. Future research should examine the role of these regions and other regulatory elements in the ontogeny of RSC-V1aR and its developmentally induced changes.

Early Intranasal Vasopressin Administration Impairs Partner Preference in Adult Male Prairie Voles (Microtus ochrogaster).

Research supports a modulatory role for arginine vasopressin (AVP) in the expression of socially motivated behaviors in mammals. The acute effects of AVP administration are demonstrably pro-social across species, providing the justification for an ever-increasing measure of clinical interest over the last decade. Combining these results with non-invasive intranasal delivery results in an attractive system for offering intranasal AVP (IN-AVP) as a therapeutic for the social impairments of children with autism spectrum disorder. But, very little is known about the long-term effects of IN-AVP during early development. In this experiment, we explored whether a single week of early juvenile administration of IN-AVP (low = 0.05 IU/kg, medium = 0.5 IU/kg, high = 5.0 IU/kg) could impact behavior across life in prairie voles. We found increases in fecal boli production during open field and novel object recognition testing for the medium dose in both males and females. Medium-dose females also had significantly more play bouts than control when exposed to novel conspecifics during the juvenile period. Following sexual maturity, the medium and high doses of IN-AVP blocked partner preference formation in males, while no such impairment was found for any of the experimental groups in females. Finally, the high-dose selectively increased adult male aggression with novel conspecifics, but only after extended cohabitation with a mate. Our findings confirm that a single week of early IN-AVP treatment can have organizational effects on behavior across life in prairie voles. Specifically, the impairments in pair-bonding behavior experienced by male prairie voles should raise caution when the prosocial effects of acute IN-AVP demonstrated in other studies are extrapolated to long-term treatment.

Dynamic corticostriatal activity biases social bonding in monogamous female prairie voles.

Summary paragraphAdult pair bonding involves dramatic changes in the perception and valuation of another individual1. One key change is that partners come to reliably activate the brain's reward system2-6, though the precise neural mechanisms by which partners become rewarding during sociosexual interactions leading to a bond remain unclear. Using a prairie vole model of social bonding7, we show how a functional circuit from medial prefrontal cortex (mPFC) to nucleus accumbens (NAcc) is dynamically modulated to enhance females' affiliative behavior towards a partner. Individual variation in the strength of this functional connectivity, particularly after the first mating encounter, predicts how quickly animals begin affiliative huddling with their partner. Rhythmically activating this circuit in a social context without mating biases later preference towards a partner, indicating that this circuit's activity is not just correlated with how quickly animals become affiliative but causally accelerates it. These results provide the first dynamic view of corticostriatal activity during bond formation, revealing how social interactions can recruit brain reward systems to drive changes in affiliative behavior.

Alcohol's effects on pair bond maintenance in male prairie voles

Alcohol abuse can have devastating effects on social relationships. In particular, discrepant patterns of heavy alcohol consumption are associated with increased rates of separation and divorce. Previous studies have attempted to model these effects of alcohol using socially monogamous prairie voles. These studies showed that alcohol consumption can inhibit the formation of pair bonds in this species. While these findings indicated that alcohol’s effects on social attachments can involve biological mechanisms, the formation of pair bonds does not properly model long-term human attachments. To overcome this caveat, the current study explored whether discordant or concordant alcohol consumption between individuals within established pairs affects maintenance of pair bonds in male prairie voles. Male and female prairie voles were allowed to form a pair bond for one week. Following this one-week cohabitation period, males received access to 10% continuous ethanol; meanwhile, their female partners had access to either alcohol and water or just water. When there was a discrepancy in alcohol consumption, male prairie voles showed a decrease in partner preference. Conversely, when concordant drinking occurred, males showed no inhibition in partner preference. Further analysis revealed a decrease in oxytocin immunoreactivity in the paraventricular nucleus of alcohol-exposed males that was independent of the drinking status of their female partners. On the other hand, only discordant alcohol consumption resulted in an increase of FosB immunoreactivity in the periaqueductal gray of male voles, a finding suggesting a potential involvement of this brain region in the effects of alcohol on maintenance of pair bonds. Our studies provide the first evidence that alcohol has effects on established pair bonds and that partner drinking status plays a large role on these effects.