Alcohol Preference and Cognitive Function

酒精偏好和认知功能

基本信息

批准号：
6867205
负责人：
Galen R Wenger
金额：
$ 24.68万
依托单位：
UNIV OF ARKANSAS FOR MED SCIS
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-01-01 至 2009-12-31
项目状态：
已结题

项目摘要

A number of studies have shown altered cognitive function in humans who abuse ethanol and other drugs of abuse. However, it is not clear whether these differences existed prior to the abuse or whether the differences are the result of the abuse. An initial approach to answering this question is to examine cognitive function in animals with known differences in preference for an abused substance, alcohol. If differences in memory and learning can be demonstrated and shown to be associated with alcohol preference, it would suggest a possible genetic association between altered memory and learning function and alcohol preference. Such a finding could provide insight into the possible role of cognitive differences observed in humans that abuse ethanol. Selective breeding has produced strains of rats with either high (P, HAD1, HAD2) or low preference (NP, LAD1, LAD2) for ethanol. The major research focus with these rats has been the documentation of their ethanol preference difference. However, there have been a few studies indicating that these rat strains may display altered cognitive function. Thus this project will examine the performance of rats with high alcohol preference (P, HAD1, HAD2) and rats with low alcohol preference ( NP, LAD1, LAD2) rats in an operant model of working memory and two models of repeated learning. Prior to the initiation of these tests of cognitive function, the degree of motivation of the rats to lever press for food presentation will be assessed under a progressive ratio schedule. If motivation differences are detected, an attempt to reduce the differences in motivation will be conducted by adjusting body weights. Once motivational factors have been normalized, the working memory and learning performance of the rats will be examined. The performance of the rats will be assessed under control conditions and following doses of ethanol, diazepam, scopolamine and methscopolamine. Ethanol was selected because of its reported effect on short-term memory in humans and laboratory animals and because of the reported differences in preference between the strains. Diazepam was selected because of its known effects on cognitive function and action at the GABA receptor. Scopolamine was selected because it is a prototype amnesic agent believed to act via cholinergic rather than GABA systems. Methscopolamine will be studied to control for peripheral actions of scopolamine. If it can be shown that differences in the cognitive function of the rats is associated with alcohol preference or non-preference, it will provide additional potential insight into the role that cognitive processes play in alcohol dependence, and possibly open new treatment avenues

许多研究表明，滥用乙醇和其他滥用药物的人的认知功能会发生改变。然而，尚不清楚这些差异是否在滥用之前就存在，或者这些差异是否是滥用的结果。回答这个问题的初步方法是检查动物的认知功能，这些动物对滥用物质酒精的偏好存在已知差异。如果记忆和学习的差异能够被证明并证明与酒精偏好相关，那么就表明记忆和学习功能的改变与酒精偏好之间可能存在遗传关联。这一发现可以深入了解在滥用乙醇的人类中观察到的认知差异的可能作用。选择性育种产生了对乙醇具有高偏好（P、HAD1、HAD2）或低偏好（NP、LAD1、LAD2）的大鼠品系。这些大鼠的主要研究重点是记录它们的乙醇偏好差异。然而，有一些研究表明这些大鼠品系可能表现出认知功能改变。因此，该项目将检查高酒精偏好大鼠（P、HAD1、HAD2）和低酒精偏好大鼠（NP、LAD1、LAD2）在工作记忆操作模型和两种重复学习模型中的表现。在开始这些认知功能测试之前，将根据渐进比例方案评估大鼠按压杠杆以获取食物的动机程度。如果检测到动机差异，将尝试通过调整体重来减少动机差异。一旦动机因素正常化，将检查大鼠的工作记忆和学习表现。将在对照条件下以及在施用乙醇、地西泮、东莨菪碱和甲东莨菪碱的剂量后评估大鼠的表现。选择乙醇是因为据报道它对人类和实验动物的短期记忆有影响，并且因为据报道菌株之间的偏好存在差异。选择地西泮是因为已知它对认知功能和 GABA 受体作用有影响。选择东莨菪碱是因为它是一种原型遗忘剂，据信通过胆碱能系统而不是 GABA 系统发挥作用。将研究甲东莨菪碱以控制东莨菪碱的外周作用。如果能够证明大鼠认知功能的差异与酒精偏好或非偏好相关，那么它将为认知过程在酒精依赖中所起的作用提供更多潜在的见解，并可能开辟新的治疗途径