Impulsivity and effects of alcohol in high and low alcohol drinking rats

描述（由申请人提供）：本提案的长期目标是确定新的生物标记，以识别滥用酒精的高风险个体。滥用酒精在许多方面对社会有害，包括由于酒精的直接或间接作用而丧失生产力、增加医疗费用和人命损失。识别个体酒精滥用倾向的特征或特征可能导致治疗酒精滥用的新目标，并加强预防。滥用酒精和其他药物的人通常表现出强烈的冲动。冲动性可能促成初次使用酒精，可能促进依赖和/或可能受到酒精本身的影响。拟议中的项目将探索冲动和与饮酒有关的基因之间的关系。该项目将使用选择性饲养的大鼠来饮用高（HAD）或低（LAD）量的酒精。该项目的第一个组成部分是评估这些大鼠系的冲动基线水平。我们将采用两种冲动性度量，一种度量冲动性选择（延迟折扣），另一种度量冲动性行为（执行/不执行任务）。延迟折扣决定了延迟后给予奖励的价值降低。在这个任务中，冲动性的增加表现为对较小的即时奖励的偏好高于较大的延迟奖励。“去/不去”任务衡量的是受试者在特定线索面前不做出反应的能力。这个程序提供了许多冲动性的测量方法，包括：假警报（在不走试验期间的错误反应），效率（获得的奖励总数/按杠杆的总数），以及提示前阶段的反应（在新试验开始之前的一段时间内的反应）。我们认为，在延迟折扣和去/不去任务中，HAD大鼠的反应比LAD大鼠更冲动。在确定对这些任务的反应基线水平后，将给动物注射酒精，以确定酒精是否会影响HAD或LAD大鼠对冲动和冒险任务的反应，或不同程度地影响反应。我们假设酒精治疗会增加延迟折扣和去/不去任务的冲动反应。我们进一步假设酒精对HAD大鼠的影响比LAD大鼠更大，这表明HAD大鼠比LAD大鼠对酒精治疗更敏感。这项研究的结果将为饮酒和冲动之间的基因联系提供新的见解，可能会确定促进成瘾的特征。

DESCRIPTION (provided by applicant): The long-term objective of this proposal is to identify new biological markers that identify individuals at high risk of abusing alcohol. Abuse of alcohol is detrimental to society in numerous ways including lost productivity, increased medical costs, and loss of human life due to the direct or indirect actions of alcohol. Identifying traits or characteristics that predispose an individual to alcohol abuse may lead to novel targets for the treatment of alcohol abuse, and enhanced prevention. Individuals that abuse alcohol and other drugs commonly exhibit heightened impulsivity. Impulsivity may precipitate initial use of alcohol, may facilitate dependence and/or may be affected by alcohol itself. The proposed project will explore the relationship between impulsivity, and the genes associated with alcohol consumption. This project will use rats selectively bred to drink high (HAD) or low (LAD) amounts of alcohol. The first component of the project is to assess baseline levels of impulsivity in these rat lines. Two measures of impulsivity will be taken, one that measures impulsive choice (delay discounting), and one that measures impulsive action (Go/No-go task). Delay discounting determines the decreased value placed on rewards that are given after a delay. Increased impulsivity in this task is demonstrated by a stronger preference for smaller immediate rewards over larger delayed rewards. The Go/No-go task measures the ability of the subject to withhold a response in the presence of specific cues. This procedure provides a number of measures of impulsivity including: false-alarms (incorrect responses during No-go trials), efficiency (total number of rewards earned/total number of lever presses), and responses during the pre-cue period (responses during the period immediately preceding the beginning of a new trial). We propose that HAD rats will respond more impulsively than LAD rats in both delay discounting and go/no-go tasks. After baseline levels of responding on these tasks are established, animals will be injected with alcohol to determine if alcohol affects responding, or differentially affects responding on impulsivity and risk-taking tasks by HAD or LAD rats. We hypothesize that alcohol treatment will increase impulsive responding on both delay discounting and Go/No- go tasks. We further hypothesize that the magnitude of the alcohol effect will be larger in HAD, than LAD rats, suggesting that HAD rats are more sensitive to alcohol treatment than LAD rats. The results of this study will provide new insight into the genetic connection between alcohol drinking and impulsivity may identify characteristics that promote addiction.