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Social affiliation and alcohol drinking in rodents

啮齿动物的社会归属和饮酒

基本信息

批准号：
9419744
负责人：
Andrey E Ryabinin
金额：
$ 34.64万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-05-01 至 2022-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9419744
关键词：
Address Adult Adverse effects Affect Aggressive behavior Alcohol abuse Alcohol consumption Alcohol dependence Alcohol withdrawal syndrome Alcoholic Beverages Alcohols Amygdaloid structure Animal Model Animals Area Biological Brain Brain region Cell Nucleus Corticosterone Corticotropin-Releasing Hormone Dependovirus Dorsal Dose Emotional Estradiol Exhibits FOS gene Family Female Funding Grant Habits Health Hour Human Immunohistochemistry Individual Laboratories Laboratory Animals Lateral Literature Maintenance Marital separation Measurement Measures Mediating Memory Microtus Modeling Motor Activity Oxytocin Pair Bond Partner in relationship Peptides Plasma Prevention strategy Regulation Rodent Role Social Environment Social Interaction Social status Societies Source Surveys System Testing Time Vasopressins alcohol effect alcohol exposure alcohol testing base designer receptors exclusively activated by designer drugs differential expression drinking experience experimental study male neural correlate neuropeptide Y polypeptide C prairie vole preference problem drinker satisfaction sex social social attachment urocortin

项目摘要

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.

人类经常饮用酒精饮料来促进社交互动。另一方面，酗酒会对长期的社会依恋产生毁灭性影响。酒精对社会关系的影响机制一直难以解决。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（田鼠）来模拟，这种情况发生了变化。后来证明，田鼠中调节配对关系的机制有助于人类社会关系，表明该动物模型具有很强的构建有效性。我们已经开始研究分析社会环境对饮酒的影响，最近发现自愿饮酒对草原田鼠雌雄关系形成的显着性别依赖性影响。具体来说，自愿饮酒抑制了雄性动物伴侣偏好的形成，但促进了雌性动物伴侣偏好的形成。这些发现表明，酒精通过生物机制发挥作用，对成人的社会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突出的埃丁格-威斯特法尔核（EWcp）中的 c-Fos 表达产生性别特异性影响。本申请旨在测试 EWcp 是否有助于酒精对配对关系的影响，并进一步研究酒精对三个特定目标 (SA) 中配对关系的影响。在 SA1 中，我们将使用基于 CLARITY 的标准免疫组织化学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的几种肽和 c-Fos 的水平。在 SA2 中，我们将使用由设计药物独家激活的设计受体方法来测试 EWcp 激活在酒精对伴侣偏好影响中的因果作用。后续研究将测试 EWcp 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第一天自愿饮酒对配对关系的形成有影响，但在 SA3 中，我们将测试长期饮酒后酒精对配对关系的影响以及酒精对已经建立的配对关系的影响。