Alcohol drinking in affiliative rodents

亲缘啮齿类动物饮酒

• 批准号: 7418683
• 负责人: Andrey E Ryabinin
• 金额: $ 28.39万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-10 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7418683
• 关键词: Accounting; Address; Adolescent; Adult; Age; Aggressive behavior; Alcohol abuse; Alcohol consumption; Alcoholic Beverages; Alcohols; Animal Model; Argipressin; Biological; Breeding; CRF receptor type 2; Cessation of life; Complex; Corticotropin; Corticotropin-Releasing Hormone; Depressed mood; Disease; Divorce; Friends; Genetic Predisposition to Disease; Genotype; Grant; Hand; Housing; Individual; Laboratories; Lead; Link; Lubricants; Measures; Microtinae; Microtus; Molecular; Neuropeptides; Oxytocin; Patients; Peptides; Pilot Projects; Predisposition; Regulation; Research; Research Personnel; Rodent; Rodent Model; Social Behavior; Social Problems; Spouses; System; Testing; Vasopressins; abuse neglect; affiliative behavior; alcohol research; alcoholism/alcohol abuse; day; developmental genetics; experience; innovation; neurochemistry; novel; prairie vole; preference; programs; receptor; receptor binding; research study; social; social neuroscience; urocortin

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.

描述（由申请人提供）：饮酒和社会行为之间存在复杂的关系。有些人将酒精饮料视为“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、虐待和攻击。饮酒通常被视为克服失去朋友或配偶后悲伤的一种方式，而离婚或朋友去世后往往会出现严重的酗酒现象。酒精和社会问题的同时发生是否可能不是巧合，而是有潜在的生物学机制？本申请提出 使用新颖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释放因子（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没有表现出强烈的亲和行为，也没有表现出大量饮酒。然而，情况已经发生了变化 随着对草原田鼠和松鼠的研究不断增加，田鼠啮齿类动物确实表现出了强烈的亲和行为。有趣的是，我们的试点研究表明，草原田鼠在两瓶偏好测试中表现出较高的酒精消耗量。草原田鼠是第一个被鉴定为高酒精消费对象的遗传异质非选择性繁殖的社会啮齿动物模型，它为解决社会和群体之间的相互作用机制提供了独特的机会。 导致高酒精摄入量的生物机制。这笔探索性拨款提议开始解决这些机制问题。特别是，我们建议通过四个具体目标解决导致高酒精摄入量的社会、发育、遗传和分子机制：1）研究田鼠社会归属与饮酒之间的相关程度； 2) 研究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量的 酒精； 3）调查大量饮酒与社会归属感之间的相关性是否由基因决定； 4) 研究加压素 V1a 和 CRF2 受体是否与酗酒的遗传倾向和社会关系的测量有关。了解这种新的啮齿动物模型中导致高酒精消耗的机制可以为治疗酗酒和酒精滥用相关疾病的创新方法奠定基础，同时考虑到社会、年龄和年龄因素。 个体患者的基因型特异性。