Alcohol drinking in affiliative rodents

描述(申请人提供)：饮酒与社交行为之间存在复杂的关系。一些人认为酒精饮料是“社交润滑剂”。另一方面，酗酒和酗酒会导致严重的社会和婚姻问题，包括忽视、虐待和侵犯。饮酒通常被认为是克服失去朋友或配偶后悲伤的一种方式，而严重的酗酒往往发生在朋友离婚或死亡之后。酒精和社会问题的同时出现难道不是巧合，而是有潜在的生物学机制吗？这项申请建议使用一种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，并涉及加压素和促肾上腺皮质激素相关因子(CRF)的特定受体。社会行为和酗酒之间的联系很难用动物模型来解决，因为大多数实验室啮齿动物不会表现出强烈的从属行为，也不会表现出高酒精饮酒。然而，随着对草原田鼠和松鼠的研究增加，情况发生了变化。草原田鼠和松鼠是确实表现出强烈附属行为的微型啮齿动物。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表现出高酒精消耗量。草原田鼠是第一个识别出遗传异质性的、非选择性繁殖的高酒精摄入量的社会啮齿动物模型，它为研究导致高酒精摄入量的社会和生物机制之间的相互作用机制提供了一个独特的机会。这项探索性赠款建议开始解决这些机制。特别是，我们建议从四个具体目标来研究导致高酒精摄入量的社会、发育、遗传和分子机制：1)调查社会联系与田鼠饮酒之间的关联程度；2)调查配对饲养和隔离饲养的青春期和成年草原田鼠是否消耗不同数量的酒精；3)调查高酒精摄入量与社会联系之间的相关性是否是遗传决定的；4)研究血管加压素V1a和CRF2受体是否有助于高酒精饮酒的遗传易感性以及社会联系的衡量标准。在这个新的啮齿动物模型中，了解导致高酒精消费的机制可以为创新的治疗酒精中毒和酒精滥用相关疾病的方法奠定基础，同时考虑到单个患者的社会、年龄和基因型的特殊性。

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.