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Alcohol use disorder affects millions of people each year. Currently approved pharmacotherapies have limited success in treating this disorder. Evidence suggests that this lack of success is partly due to how these pharmacotherapies are tested in preclinical settings. The vast majority of preclinical studies assessing the effects of pharmacotherapies on alcohol or drug self-administration are done in individually housed animals. However, it is known that alcohol and drug intake are heavily influenced by social settings. Here, we adapted radio frequency tracking technology to determine the effects of oxytocin, a potential therapy for alcohol use disorder, on alcohol consumption in socially housed male and female prairie voles. Voluntary alcohol consumption in these animals resulted in high daily alcohol intakes, blood ethanol concentrations that are considered intoxicating, and central changes in FosB immunoreactivity, indicative of changes in neural activity. Prairie voles that received oxytocin temporarily reduced alcohol consumption but not alcohol preference, compared with control prairie voles regardless whether their cagemates received a similar treatment or not. Our results demonstrate that oxytocin can decrease consummatory behaviors in the presence of peers that are not receiving this treatment, and therefore, its potential use in clinical trials is warranted. Moreover, effectiveness of other pharmacotherapies in preclinical studies can be tested in mixed-treatment socially housed animals similarly to clinical studies in humans.

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AIMS: Discordant heavy alcohol use is a risk factor for disruption of intimate partner relationships. Modeling these relationships in prairie voles indicates that biological effects of alcohol can contribute to this risk. In particular, alcohol consumption disrupted an established preference for a female partner in male prairie voles if the partner was drinking water, but not if the partner was drinking alcohol. The current study investigated the effects of alcohol consumption on pair bonds in female prairie voles. METHODS: Female and male prairie voles established pair bonds during 1 week of cohabitation. Following cohabitation, females and their partners were put into mesh-divided cages where they were given access to 10% ethanol and water or only water for 1 week. Pair bonds in female prairie voles were tested using the partner preference test (PPT). Following the PPT, we examined oxytocin, vasopressin and FosB immunoreactivity across several brain regions. RESULTS: Female prairie voles consumed more alcohol if their male partner was also drinking alcohol, but not if their partner was drinking water. During PPT, females preferred their partner over a stranger, regardless of their partner's drinking status. Alcohol consumption decreased oxytocin immunoreactivity in the paraventricular nucleus of the hypothalamus and increased FosB immunoreactivity in the centrally projecting Edinger-Westphal nucleus. CONCLUSIONS: Established partner preference in female prairie voles is resistant to alcohol consumption. This finding suggests that the risk for disruption of intimate partner relationships in females is not mediated by a decreased motivation to be with their partners.

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Pathological and social consequences associated with excessive alcohol consumption and dependence constitute a serious concern for human well-being. The success of preventative and therapeutic strategies for alcohol use disorder depends on the development of appropriate animal models of alcohol consumption. Alcohol consumption in humans typically occurs in social settings. In contrast, the vast majority of animal models investigate alcohol drinking in socially isolated animals. A number of rodent model studies have attempted to assess drinking of individual animals within social setting. These studies identified varied directions of effects of social environment on alcohol consumption. However, the interpretation of these results is strongly hampered by technical issues associated with the existing approaches to assess drinking of individual animals within each group. This review analyzes the existing literature mostly focusing on the interpretation caveats of performed studies and highlights some of the new directions in these studies.

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The expression of pain serves as a way for animals to communicate potential dangers to nearby conspecifics. Recent research demonstrated that mice undergoing alcohol or morphine withdrawal, or inflammation, could socially communicate their hyperalgesia to nearby mice. However, it is unknown whether such social transfer of hyperalgesia can be observed in other species of rodents. Therefore, the present study investigated if the social transfer of hyperalgesia occurs in the highly social prairie vole (Microtus ochrogaster). We observe that adult female prairie voles undergoing withdrawal from voluntary two-bottle choice alcohol drinking display an increase in nociception. This alcohol withdrawal-induced hypersensitiity is socially transferred to female siblings within the same cage and female strangers housed in separate cages within the same room. These experiments reveal that the social transfer of pain phenomenon is not specific to inbred mouse strains and that prairie voles display alcohol withdrawal and social transfer-induced hyperalgesia.

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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, this 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 1 week. Following this 1-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 (PP). Conversely, when concordant drinking occurred, males showed no inhibition in PP. 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 in these effects.

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Pain is often described as a "biopsychosocial" process, yet social influences on pain and underlying neural mechanisms are only now receiving significant experimental attention. Expression of pain by one individual can be communicated to nearby individuals by auditory, visual, and olfactory cues. Conversely, the perception of another's pain can lead to physiological and behavioral changes in the observer, which can include induction of hyperalgesia in "bystanders" exposed to "primary" conspecifics in which hyperalgesia has been induced directly. The current studies were designed to investigate the neural mechanisms responsible for the social transfer of hyperalgesia in bystander mice housed and tested with primary mice in which hyperalgesia was induced using withdrawal (WD) from voluntary alcohol consumption. Male C57BL/6J mice undergoing WD from a two-bottle choice voluntary alcohol-drinking procedure served as the primary mice. Mice housed in the same room served as bystanders. Naïve, water-drinking controls were housed in a separate room. Immunohistochemical mapping identified significantly enhanced Fos immunoreactivity (Fos-ir) in the anterior cingulate cortex (ACC) and insula (INS) of bystander mice compared to naïve controls, and in the dorsal medial hypothalamus (DMH) of primary mice. Chemogenetic inactivation of the ACC but not primary somatosensory cortex reversed the expression of hyperalgesia in both primary and bystander mice. These studies point to an overlapping neural substrate for expression of socially transferred hyperalgesia and that expressed during alcohol WD.

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