Alcohol drinking in affiliative rodents

亲缘啮齿类动物饮酒

基本信息

批准号：
7619303
负责人：
Andrey E Ryabinin
金额：
$ 27.86万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-05-10 至 2011-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7619303
关键词：
Accounting Address Adolescent Adult Age Aggressive behavior Alcohol abuse Alcohol consumption Alcoholic Beverages Alcoholism 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 therapy developmental genetics experience innovation neurochemistry novel prairie vole preference programs receptor receptor binding research study social social neuroscience urocortin

项目摘要

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。饮酒通常被认为是克服失去朋友或失去朋友后悲伤的一种方法。配偶，以及严重酗酒经常发生在离婚或朋友死亡之后，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？本申请建议使用一种新颖的啮齿动物模型来解决这个问题。更多的具体来说，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。社会行为和酒精滥用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这样做。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以及确实表现出强烈亲和的啮齿动物的研究的增加，情况发生了变化。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。作为第一个确定的高酒精摄入量的遗传异质非选择性繁殖的社会啮齿动物模型，草原田鼠为解决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独特的机会。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）调查配对饲养和隔离饲养的青春期和成年草原田鼠的饮酒量是否不同； 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归属感有关。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酒精中毒和酒精滥用相关疾病的创新方法奠定基础，同时考虑到个体患者的社会、年龄和基因型特异性。