Socially-facilitated excessive alcohol drinking in a novel prairie vole model

新型草原田鼠模型中社交促进的过量饮酒

• 批准号: 8059285
• 负责人: Allison MJ Anacker
• 金额: $ 4.14万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8059285
• 关键词: Address; Adolescence; Adolescent; Affect; Age; Alcohol abuse; Alcohol consumption; Alcoholism; Alcohols; Amygdaloid structure; Animal Model; Animals; Area; Argipressin; Autoradiography; Back; Behavior; Behavioral; Binding; Biological; Biological Factors; Brain; Brain region; Communication; Complex; DNA; Dose; Environmental Risk Factor; Exhibits; Genetic; Genetic Polymorphism; Globus Pallidus; Health; Heavy Drinking; Housing; Individual; Influentials; Intake; Laboratories; Lead; Legal; Length; Life; Ligands; Link; Mediator of activation protein; Microsatellite Repeats; Microtus; Modeling; Monitor; Mus; Neuropeptides; Outcome; Pair Bond; Pattern; Peer Pressure; Polymerase Chain Reaction; Population; Prevention; Rattus; Regulation; Relative (related person); Research; Rodent; Role; Sampling; Social Behavior; Social Dominance; Social Interaction; Social isolation; Societies; System; Tail; Testing; Time; Tube; V1a vasopressin receptor; Vasopressin Antagonist; Vasopressin Receptor; Water; Work; alcohol measurement; alcohol use disorder; base; behavior influence; binge drinking; college; density; drinking; drinking behavior; dyadic interaction; member; novel; olfactory bulb; prairie vole; preference; prevent; promoter; public health relevance; receptor; receptor binding; social; social attachment; supraoptic nucleus; treatment strategy

DESCRIPTION (provided by applicant): Socially-facilitated excessive drinking is common in adolescence, and social relationships remain a primary factor in alcohol intake throughout life. Patterns of social binge drinking can have many direct negative consequences, and have the potential to lead to later alcohol abuse. By understanding the biological and social influences on excessive drinking we can begin to prevent and treat alcohol use disorders. The objective of the proposed studies is to understand the effects of social affiliations on alcohol drinking in a novel animal model for this behavior, the prairie vole, which exhibits strong social bonds and a naturally high intake of alcohol. This objective will be addressed with the following three aims: 1 Elucidate dyadic interactions in patterns of alcohol intake, and their effects on drinking levels. To test the social influence on alcohol intake patterns, 'high drinkers' will be paired with 'low drinkers,' designated as such during a two-bottle choice test with water and 10% alcohol in social isolation. The alcohol intake of each animal will be monitored using a lickometer system, to determine whether the drinking level of one or both animals changes in the paired condition. Subsequently, alcohol intake in a second isolation will be assessed to determine whether changes in drinking during social housing persist even without continuing social influence. Further, the pattern of drinking of each vole will be assessed to determine whether there are social interactions influencing timing of drinking such as one animal drinking before the other, or simultaneous drinking. 2 Determine whether social dominance is linked with influential drinking behavior. As in 1, high and low drinkers will be paired to assess drinking. Before pairing, the voles will be introduced in the social dominance tube task to determine which vole exhibits more dominant behavior, evidenced by pushing the other animal back to its starting cage through a narrow tube. Association between dominance and initial drinking level, propensity to adjust alcohol preference, and propensity to initiate drinking bouts will be assessed. 3 Determine whether vasopressin V1a receptor microsatellite length or binding level affects social drinking or dominance behavior. DNA samples acquired from tails from the animals used in 1 and 2 will be used to determine microsatellite length by amplification of the region within the V1aR promoter using polymerase chain reaction, followed by fragment length analysis. Brains from the same animals will be used to determine V1aR binding level by autoradiography, using a 125I- linear-AVP antagonist as a ligand for the V1aR. Then correlations between microsatellite length or receptor binding density in discrete brain regions and initial drinking level, change in alcohol intake, and dominance behavior will be analyzed to determine whether this genetic factor or receptor levels correspond with social and drinking behaviors. Discovery of social factors that can directly affect alcohol drinking behavior, or genetic factors that can influence social and/or alcohol drinking behavior is important in furthering understanding of the emergence or progression of alcoholism, and in developing new prevention or treatment strategies. PUBLIC HEALTH RELEVANCE: Alcohol use disorders are a prevalent problem that can lead to health, financial, social, and legal problems that affect not only individuals but society as a whole. The proposed work seeks to understand and ultimately prevent or treat the progression from social drinking to alcohol abuse, by uncovering biological and environmental factors that influence alcohol intake in an animal model of socially-facilitated excessive alcohol drinking.

描述（由申请人提供）：在青春期中，社会上有足够的过度饮酒很普遍，社会关系仍然是一生中酒精摄入量的主要因素。社交暴饮暴食的模式可能会带来许多直接的负面后果，并有可能导致后来的酗酒。通过了解对过度饮酒的生物学和社会影响，我们可以开始预防和治疗酒精使用障碍。拟议的研究的目的是了解这种行为的新动物模型中社会隶属关系对饮酒的影响，草原沃尔（Prairie Vole）表现出牢固的社会纽带和天然高的酒精摄入量。该目标将以以下三个目的来解决：1个阐明酒精摄入方式中的二元相互作用及其对饮酒水平的影响。为了测试对酒精摄入模式的社会影响，“高饮酒者”将与“低饮酒者”配对，并在两瓶选择测试中被指定为水，在社会隔离中进行了10％的酒精。每种动物的酒精摄入量将使用舔系统进行监测，以确定一种或两只动物的饮酒水平是否在配对状态下发生变化。随后，将评估第二次隔离的酒精摄入量，以确定即使没有持续的社会影响力，社会住房期间饮酒的变化是否仍然存在。此外，将评估每种vole的饮用方式，以确定是否存在社交互动影响饮酒的时机，例如一种动物饮酒，或者同时喝酒。 2确定社会优势是否与有影响力的饮酒行为有关。与1一样，饮酒量将配对，以评估饮酒。在配对之前，将在社会优势管任务中引入田鼠，以确定哪种vole表现出更大的占主导地位，这证明了通过将另一只动物推回到狭窄的管子的起始笼子中。优势和初始饮酒水平，调整酒精偏好的倾向以及发起饮酒爆发的倾向之间的关联将得到评估。 3确定加压素V1A受体微卫星长度或结合水平是否会影响社会饮酒或优势行为。从1和2中使用的动物中获取的DNA样品将用于通过使用聚合酶链反应在V1AR启动子内扩增微卫星长度，然后进行片段长度分析。同一动物的大脑将使用125-linear-AVP拮抗剂作为V1AR的配体来确定通过放射自显影的V1AR结合水平。然后将分析微卫星长度或受体结合密度之间的相关性与初始饮酒水平，酒精摄入量的变化以及优势行为之间的相关性，以确定这种遗传因素或受体水平是否与社交和饮酒行为相对应。发现可以直接影响饮酒行为的社会因素，或者可能影响社会和/或饮酒行为的遗传因素在进一步了解酒精中毒的出现或进展以及制定新的预防或治疗策略方面很重要。 公共卫生相关性：酒精使用障碍是一个普遍的问题，它可能导致健康，财务，社会和法律问题不仅影响个人，而且影响整个社会。拟议的工作试图通过揭示影响社会化的过量酒精饮酒的动物模型中影响酒精摄入的生物学和环境因素，以理解并最终预防或治疗从社会饮酒到酒精滥用的进展。