Alcohol drinking in affiliative rodents

描述（由申请人提供）：饮酒和社会行为有着复杂的关系。有些人认为酒精饮料是“社会润滑剂”。另一方面，酗酒和酗酒导致严重的社会和婚姻问题，包括忽视、虐待和攻击。酒精消费通常被认为是一种克服失去朋友或配偶后悲伤的方法，严重的酒精滥用通常发生在离婚或朋友去世后。酒精和社会问题的同时出现可能不是巧合，而是有潜在的生物学机制吗？本申请提出使用新的啮齿动物模型来解决这个问题。更具体地说，我们假设调节社会行为和酒精摄入的神经化学机制重叠，并涉及特定的受体加压素和促肾上腺皮质激素释放因子（CRF）。社会行为和酒精滥用之间的联系一直很难用动物模型来解决，因为大多数实验室啮齿动物没有表现出强烈的亲和行为，也没有表现出大量饮酒。然而，随着对草原田鼠和松田鼠研究的增加，这种情况发生了变化，这些田鼠确实表现出强烈的亲和行为。有趣的是，我们的初步研究表明，草原田鼠在两瓶偏好测试中显示出高酒精消耗。作为第一个确定的遗传异质性非选择性繁殖的社会啮齿动物模型的主题与高酒精消费，草原田鼠提供了一个独特的机会，以解决社会和生物机制之间的相互作用机制，导致高酒精摄入量。这项探索性赠款提议开始处理这些机制。特别是，我们提出了四个具体目标来解决导致高酒精摄入的社会、发育、遗传和分子机制：1）调查社会关系与田鼠饮酒之间的相关程度; 2）调查配对和隔离饲养的近青春期和成年草原田鼠是否消耗不同数量的酒精; 3）研究高酒精摄入量和社会关系之间的相关性是否由遗传决定; 4）研究加压素V1 a和CRF 2受体是否有助于高酒精饮酒的遗传易感性和社会关系的测量。了解这种新的啮齿动物模型中导致高酒精消费的机制可以为考虑到个体患者的社会，年龄和基因型特异性的酒精中毒和酒精滥用相关疾病的治疗创新方法奠定基础。

DESCRIPTION (provided by applicant): Alcohol consumption and social behaviors have a complex relationship. Some view alcoholic beverages as 'social lubricants". On the other hand, alcohol abuse and alcoholism lead to severe social and marital problems, including neglect, abuse and aggression. Alcohol consumption is often regarded as a way to overcome sadness following loss of friend or spouse, and severe alcohol abuse often follows divorce or death of friend. Could the co-occurrence of alcohol and social problems be not a coincidence, but have an underlying biological mechanism? This application proposes to use a novel rodent model to address this question. More specifically, we hypothesize that neurochemical mechanisms regulating social behaviors and alcohol intake overlap and involve specific receptors to vasopressin and corticotropin-relasing factor (CRF). The link between social behavior and alcohol abuse has been difficult to address using animal models because most laboratory rodents don't display strong affiliative behaviors and don't show high alcohol drinking. However, the situation has changed with increased research on prairie and pine voles, microtine rodents that do display strong affiliative behaviors. Intriguingly, our pilot studies indicate that prairie voles show high alcohol consumption in a two-bottle preference test. Being the first identified genetically heterogeneous non-selectively bred social rodent model of subjects with high alcohol consumption, the prairie voles offer a unique opportunity to address the mechanisms of interactions between social and biological mechanisms leading to high alcohol intake. This exploratory grant proposes to begin addressing these mechanisms. In particular, we propose to address social, developmental, genetic and molecular mechanisms leading to high alcohol intake in four specific aims: 1) To investigate the extent of correlation between social affiliation and alcohol drinking in voles; 2) To investigate whether pair-housed and isolate-housed peri-adolescent and adult prairie voles consume different amounts of alcohol; 3) To investigate whether the correlation between high alcohol intake and social affiliation is genetically determined; 4) To investigate whether vasopressin V1a and CRF2 receptors contribute to genetic predisposition to high alcohol drinking and measures of social affiliation. Understanding mechanisms leading to high alcohol consumption in this new rodent model could lay ground for innovative approaches to treatment of alcoholism and alcohol abuse-related disorders taking into account the social-, age- and genotype-specific particularities of an individual patient.