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志物，以识别滥用酒精的高风险个体。酒精滥用在许多方面对社会有害，包括生产力损失，医疗费用增加，以及由于酒精的直接或间接作用而导致的人类生命损失。识别使个体易于酒精滥用的特征或特征可能会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高度的冲动。冲动可能会促使初次使用酒精，可能会促进依赖和/或可能受到酒精本身的影响。该项目将探索冲动性和与酒精消费相关的基因之间的关系。该项目将使用选择性饲养的大鼠，以饮用高（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品系的冲动基线水平。将采取两种冲动性措施，一种是衡量冲动选择（延迟折扣），另一种是衡量冲动行为（去/不去任务）。延迟折扣确定延迟后给予的奖励的减少值。在这项任务中，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。Go/No-go任务测量受试者在特定线索存在下保留反应的能力。这个程序提供了许多冲动性的测量方法，包括：假警报（在不通过试验期间的不正确反应），效率（获得的奖励总数/杠杆按压总数），以及在提示前期间的反应（在新试验开始之前的时间段内的反应）。我们建议，HAD大鼠将比LAD大鼠在延迟折扣和去/不去任务更冲动的反应。在建立对这些任务的响应的基线水平后，将用酒精注射动物以确定酒精是否影响响应，或对HAD或LAD大鼠的冲动性和冒险任务的响应产生差异性影响。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，酒精的影响程度将在HAD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遗传联系提供新的见解，可以识别促进成瘾的特征。

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.