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.

人类经常食用酒精饮料来促进社会互动。另一方面，酗酒可能会对长期社会依恋产生毁灭性影响。酒精对社会关系的影响很难解决。情况随着研究的变化，表明可以使用社会一夫一妻制田鼠（Microtus ochrogaster）对社会联系的许多特征进行建模。调节田鼠的配对键合的机制后来被证明有助于人类的社会纽带，表明该动物模型的强大构造有效性。我们已经开始研究分析社会环境对饮酒的影响，最近发现了自愿饮酒对草原田鼠男性女性纽带形成的显着性依赖性影响。具体而言，自愿性饮酒抑制了雄性动物的伴侣偏爱的形成，但促进了女性的伴侣偏好。这些发现表明，酒精通过生物学机制作用，对成人社会依恋产生特定影响。同时，我们发现同居期间的饮酒还会在中央射击的Edinger-Westphal核（EWCP）中对C-FOS表达产生性别特异性影响。该应用建议测试EWCP是否有助于酒精对配对键的影响，并进一步研究酒精对三个特定目的（SAS）配对键的影响。在SA1中，我们将在存在或不存在酒精的情况下使用基于明确的和标准的免疫组织化学来测量不同大脑区域的几种肽和C-FOS的水平。在SA2中，我们将使用Designer Drugs方法仅激活的设计器受体（S）来测试EWCP激活在酒精对伴侣偏好效果中的因果作用。随后的研究将测试SA1中确定的EWCP或大脑区域的特定亚群的作用。最后，尽管我们以前的研究发现了自愿饮酒对成对键的第一天的影响，但在SA3中，我们将测试酒精对长期使用酒精使用和酒精对已经建立的配对键的影响后对醇对配对键的影响。