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

描述(申请人提供)：社交促成的过度饮酒在青春期很常见，社会关系仍然是终生饮酒的主要因素。社交狂饮的模式可能会产生许多直接的负面后果，并有可能导致后来的酗酒。通过了解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。这项拟议的研究的目的是在一种新的动物模型-草原田鼠中了解社会背景对饮酒的影响，草原田鼠表现出强大的社会纽带和天生的高酒精摄入量。这一目标将通过以下三个目标来实现：1阐明酒精摄取模式中的二元相互作用及其对饮酒水平的影响。为了测试社会对饮酒模式的影响，“高饮酒者”将与“低饮酒者”配对，在与社会隔离的两瓶水和10%酒精的选择测试中，低饮酒者被指定为“低饮酒者”。每只动物的酒精摄入量将使用舔舌计系统进行监测，以确定其中一只或两只动物的饮酒水平在配对条件下是否发生变化。随后，将对第二次隔离期间的酒精摄入量进行评估，以确定即使没有持续的社会影响，社会住房期间饮酒的变化是否会持续下去。此外，还将评估每只田鼠的饮酒模式，以确定是否存在影响饮酒时间的社会互动，如一只动物先于另一只动物饮酒，或同时饮酒。2确定社交优势是否与有影响力的饮酒行为有关。与第一项一样，高饮酒者和低饮酒者将被配对评估饮酒情况。在配对之前，这些田鼠将被引入社会支配管任务，以确定哪只田鼠表现出更具优势的行为，证据是通过一个狭窄的管将另一只动物推回它的起始笼子。将评估支配地位与初始饮酒水平、调整饮酒偏好的倾向以及发起饮酒比赛的倾向之间的关系。3确定加压素V1a受体微卫星长度或结合水平是否影响社交饮酒或支配行为。从1和2中使用的动物的尾巴中获得的DNA样本将用于通过聚合酶链式反应扩增V1aR启动子区域来确定微卫星长度，然后进行片段长度分析。来自相同动物的大脑将被用来通过放射自显影来确定V1aR的结合水平，使用125I-线性AVP拮抗剂作为V1aR的配体。然后分析不同脑区的微卫星长度或受体结合密度与初始饮酒水平、饮酒变化和优势行为的相关性，以确定这些遗传因素或受体水平是否与社交和饮酒行为相对应。发现可直接影响饮酒行为的社会因素，或可影响社会和/或饮酒行为的遗传因素，对于进一步了解酒精中毒的发生或发展，以及开发新的预防或治疗策略具有重要意义。 公共卫生相关性：酒精使用障碍是一个普遍存在的问题，可能会导致健康、经济、社会和法律问题，不仅影响个人，而且影响整个社会。这项拟议的工作试图通过揭示在社会促成的过度饮酒的动物模型中影响酒精摄入量的生物和环境因素，来了解并最终防止或治疗从社交饮酒到酗酒的进展。

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.