GENETIC ASPECTS OF ALCOHOLS BEHAVIORAL ACTIVATION

酒精行为激活的遗传方面

基本信息

批准号：
2045246
负责人：
BRUCE C. DUDEK
金额：
$ 17.18万
依托单位：
STATE UNIVERSITY OF NEW YORK AT ALBANY
依托单位国家：
美国
项目类别：
财政年份：
1991
资助国家：
美国
起止时间：
1991-08-01 至 1999-07-31
项目状态：
已结题

项目摘要

One of the hallmarks of alcohol's many actions is it's frequent biphasic effect. Low doses often produce activation of behavioral and physiological characters. The behavioral activation is variously described as a stimulant effect, euphoria, and disinhibition. Although clear resolution of its dimensions is not yet available, such activating effects are now receiving focus in some genetically based theories of alcoholism. In Cloninger's scheme of alcoholic subtypes, Type II is argued to use alcohol for these euphoriant effects, implying a genetically based sensitivity to this domain of ethanol action. A general working hypothesis states that these activational effects are somehow related to the abuse potential of ethanol, and therefore represent an important addiction liability. A small literature on neurobiological aspects of the activation effect implicate brain dopamine systems, one neurotransmitter known to be important in brain reward systems. Laboratory studies of behavioral activation by ethanol have shown clear genetic influences on this type of initial sensitivity. Mouse locomotor activity has been the most highly investigated phenotype for this question of ethanol activation. The studies outlined here have three general goals. The first is the use of detailed breeding studies to continue our genetic characterization of the activational effect. Our work has suggested that a simple genetic system with as few as three genes might influence this character, and several breeding designs will further test this hypothesis. The second goal is the production of congenic strains of mice where the genetic alleles producing activation in three different stocks, are backcrossed onto the background of the C57BL/6 strain which shows no ethanol-induced activation. Congenic strains are an extremely powerful technique, not heretofore used in alcohol research. They will, in the future, permit tests of specific hypotheses concerning the behavioral, and neurobiological foundations of ethanol's activating actions, and provide a strong tool for mapping and molecular biological study. A third goal involves characterizing the psychopharmacological phenomenology of the paradoxical activational effect of ethanol. We are attempting to define the range of behaviors, such as aggressive behavior, which are commonly genetically influenced in the domain of these activational effects of ethanol.

酒精许多动作的标志之一是它经常出现双相影响。低剂量通常会产生行为的激活和生理特征。行为激活是各种各样的被描述为一种刺激效果，欣快和抑制作用。虽然尚未清楚其尺寸的分辨率，例如激活效果现在在某些基于遗传学的理论中得到了重点酗酒。在克洛宁格的酒精亚型方案中，II型为主张将酒精用于这些兴奋的效果，这意味着遗传基于对乙醇作用领域的敏感性。一般工作假设指出，这些活化效应与乙醇的滥用潜力，因此代表了重要的成瘾责任。关于神经生物学方面的小文献激活效应暗示脑多巴胺系统，一个神经递质已知在大脑奖励系统中很重要。乙醇行为激活的实验室研究表明遗传对这种初始灵敏度的影响。鼠标运动活动一直是该问题最受研究的表型乙醇激活。这里概述的研究有三个一般目标。首先是使用详细的育种研究继续我们活化效应的遗传表征。我们的工作有提出一个只有三个基因的简单遗传系统可能影响这个角色，几种繁殖设计将进一步测试这个假设。第二个目标是生产先天性菌株遗传等位基因在三种不同的遗传等位基因中产生活化的小鼠库存，将串交给C57BL/6菌株的背景没有显示乙醇诱导的激活。先天性菌株非常强大的技术，而不是迄今为止用于酒精研究的技术。他们会，将来，允许对有关的特定假设进行测试乙醇激活的行为和神经生物学基础动作，并为映射和分子生物学提供了强大的工具学习。第三个目标涉及表征心理药理学乙醇悖论活化作用的现象学。我们是试图定义行为的范围，例如侵略行为，通常在这些领域受到遗传影响乙醇的活化作用。