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

描述(由申请人提供)：这项提议的长期目标是确定新的生物标记，以识别高风险滥用酒精的个人。滥用酒精在许多方面对社会造成危害，包括丧失生产力、增加医疗费用，以及因酒精的直接或间接作用而造成的生命损失。确定使个人容易酗酒的特征或特征可能会导致治疗酗酒和加强预防的新目标。滥用酒精和其他药物的人通常表现出高度的冲动。冲动可能导致酒精的初次使用，可能促进依赖和/或可能受到酒精本身的影响。这项拟议的项目将探索冲动与饮酒相关基因之间的关系。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。该项目的第一部分是评估这些大鼠品系的基线冲动水平。将采取两种衡量冲动的方法，一种是衡量冲动选择(延迟折扣)，另一种是衡量冲动行为(进行/不进行任务)。延迟折扣决定了延迟后给予的奖励的减少值。在这项任务中增加的冲动表现为对较小的即时奖励的更强烈的偏好，而不是较大的延迟奖励。进行/不进行任务衡量的是受试者在出现特定提示时抑制反应的能力。这一程序提供了许多冲动的衡量标准，包括：错误警报(拒绝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)和提示前期间的反应(紧接新试验开始前的反应)。我们认为，在延迟折扣和进行/不进行任务中，HAD大鼠的反应都比LAD大鼠更冲动。在建立了对这些任务的反应的基线水平后，将向动物注射酒精，以确定酒精是否影响反应，或者对HAD或LAD大鼠的冲动和冒险任务的反应产生不同的影响。我们假设酒精处理会增加延迟折扣和进行/不进行任务的冲动反应。我们进一步假设HAD的酒精效应将比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研究饮酒和冲动之间的遗传联系提供新的见解，可能会识别出促进成瘾的特征。

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.