Social affiliation and alcohol drinking in rodents

人们经常饮用酒精饮料来促进社会交往。另一方面，酗酒会对长期的社会依恋产生毁灭性的影响。酒精对社会关系的影响机制一直难以解决。随着研究表明社会联系的许多特征可以用社会一夫一妻制的草原田鼠（Microtus ochrogaster）来模拟，情况发生了变化。调节田鼠配对的机制后来被证明有助于人类的社会联系，这表明这种动物模型具有很强的结构效度。 我们已经开始研究分析社会环境对酒精消费的影响，最近，发现自愿饮酒对草原田鼠男女关系形成的显著性别依赖影响。具体而言，自愿饮酒抑制形成的合作伙伴偏好的雄性动物，但促进合作伙伴偏好的女性。这些发现表明，酒精通过生物学机制对成年人的社会依恋产生特定的影响。与此同时，我们发现，在同居期间饮酒也产生性别特异性的影响c-Fos的表达在中央突出的Edinger-Westphal核（EWcp）。本申请旨在测试EWcp是否有助于酒精对成键的影响，并进一步研究酒精对三种特定目标（SA）中成键的影响。在SA 1中，我们将使用基于免疫组织化学的标准免疫组织化学方法来测量在存在或不存在酒精的情况下同居期间不同大脑区域中几种肽和c-Fos的水平。在SA 2中，我们将使用设计师受体（S）仅由设计师药物（S）激活的方法来测试EWcp激活在酒精对伴侣偏好影响中的因果作用。随后的研究将测试EWcp的特定亚群或在SA 1中鉴定的脑区域的作用。最后，虽然我们之前的研究发现了自愿饮酒的第一天对配对债券形成的影响，但在SA 3中，我们将测试长期饮酒后酒精对配对债券的影响以及酒精对已经建立的配对债券的影响。

Humans often consume alcoholic beverages to promote social interactions. On the other hand, alcohol abuse can have devastating effects on long-term social attachments. The mechanisms alcohol's effects on social relationships have been difficult to address. The situation changed with studies showing that many features of social bonding can be modeled using socially monogamous prairie voles (Microtus ochrogaster). Mechanisms regulating pair bonding in voles have later been shown to contribute to human social bonding, indicating strong construct validity of this animal model. We have initiated studies analyzing effects of social environment on alcohol consumption and, more recently, identified striking sex-dependent effects of voluntary alcohol consumption on the formation of male-female bonds in prairie voles. Specifically, voluntary alcohol consumption inhibited formation of partner preference in male animals, but facilitated partner preference in females. These findings indicated that alcohol acts through biological mechanisms to produce specific effects on adult social attachments. In parallel we found that alcohol drinking during cohabitation also produces sex-specific effects on c-Fos expression in the centrally-projecting Edinger-Westphal nucleus (EWcp). This application proposes to test whether EWcp contributes to alcohol's effects on pair bonding and further investigate alcohol's effects on pair bonding in three Specific Aims (SAs). In SA1 we will use CLARITY-based and standard immunohistochemistry to measure levels of several peptides and c-Fos across different brain regions during cohabitation in the presence or absence of alcohol. In SA2 we will test the causal role of EWcp activation in alcohol's effects on partner preference using the Designer Receptor(s) Exclusively Activated by Designer Drug(s) approach. Subsequent studies will test the roles of specific subpopulations of EWcp or brain regions identified in SA1. Finally, while our previous studies found effects of the first day of voluntary alcohol drinking on formation of pair-bonds, in SA3 we will test alcohol's effects on pair bonding following prolonged alcohol use and alcohol's effects on already established pair bonds.