Social affiliation and alcohol drinking in rodents

人类经常饮用酒精饮料来促进社交互动。另一方面，酗酒可能会对长期的社交依恋产生毁灭性的影响。酒精对社会关系的影响机制一直很难解决。随着研究表明，社会纽带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。调节田鼠配对结合的机制后来被证明有助于人类的社会联系，这表明这个动物模型的结构有效性很强。 我们已经开始了分析社会环境对饮酒影响的研究，最近，我们发现自愿饮酒对草原田鼠形成雌雄结合的显著性别依赖效应。具体地说，自愿饮酒抑制了雄性动物伴侣偏好的形成，但促进了雌性动物的伴侣偏好。这些发现表明，酒精通过生物机制对成年人的社交依恋产生特定的影响。与此同时，我们发现，同居期间饮酒也会对中央投射的Edinger-Westphal核(EWCP)的c-Fos表达产生性别特异性影响。这项申请建议测试EWCP是否有助于酒精对配对结合的影响，并进一步研究酒精对三个特定目标(SA)的配对结合的影响。在SA1中，我们将使用基于透明和标准的免疫组织化学来测量在酒精存在或不存在的情况下同居期间不同大脑区域的几种多肽和c-Fos的水平。在SA2中，我们将使用由设计师药物(S)独家激活的设计师受体(S)方法来检验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SA1中确定的大脑区域的作用。最后，虽然我们之前的研究发现，自愿饮酒的第一天对配对键的形成有影响，但在SA3中，我们将测试酒精对长期饮酒后配对结合的影响，以及酒精对已经建立的配对键的影响。

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.