Activating Effects of Ethanol in Selectively Bred Rats

乙醇对选择性饲养大鼠的激活作用

• 批准号: 7125161
• 负责人: JAMES M MURPHY
• 金额: $ 17.95万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-26 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7125161
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; behavioral /social science research tag; behavioral genetics; craving; dosage; ethanol; genetic strain; genetic susceptibility; heart rate; laboratory rat; reinforcer; self medication; substance abuse related behavior

DESCRIPTION (provided by applicant): Behavioral and biological phenotypes of alcohol abuse and alcoholism have been described, investigated and reported in the literature for decades. In contemporary experimental literature, there has been considerable effort toward discovering hereditary factors that are ultimately expressed phenotypically as predispositions or susceptibilities to alcohol abuse. Knowledge in this arena has been advanced considerably by research both in humans and in animal models of alcohol abuse and alcoholism but, in many cases, it has been difficult to draw meaningful parallels between the findings from human studies and that of animal research. This proposal focuses on an evaluation of the overall premise that the reinforcing effects of alcohol are reflected in, and are mediated partly by, phenotypic responses, and that these phenotypes include behavioral (e.g., locomotor) and autonomic activation. In recent studies, we have investigated heart rate (HR) as an index of autonomic activity that represents some distinctive profiles consequent to alcohol administration and alcohol ingestion (Bell et al., 2002). The proposed experiments seek to extend these findings and to test hypotheses concerning whether, and the extent to which, behavioral and HR reactions to alcohol's reinforcing properties result, at least in part, from hereditary predispositions to excessive alcohol self-administration. Another goal is to assess whether these phenotypic characterizations could prove to be useful, objective measures in evaluating theoretical assumptions on the behavioral and neurobiological substrates of alcohol's reinforcing efficacy, which could assist in pharmacotherapy development. To accomplish these goals, experiments in four Specific Aims will investigate in selectively bred rats (1) behavioral and HR dose-response effects of ethanol administration, (2) behavioral and HR activating effects of self-administered ethanol in free-choice drinking, (3) behavioral and HR activating effects of self-administered ethanol in an operant paradigm designed to evaluate periods of anticipation, extinction, and recovery of responding, and (4) behavioral and HR activating effects of intracranially self-administered ethanol directly into the ventral tegmental area of the brain in order to provide an evaluation of potential neurobiological substrates mediating these behavioral phenotypes. The findings will serve to evaluate, expand and validate the proposed measures as phenotypic associations within animal models of excessive alcohol-seeking behavior and will provide potential empirical parallels of characterized phenotypes in human alcoholics and those who are predisposed to alcohol abuse and alcoholism.

描述（由申请人提供）：数十年来，已经在文献中描述，调查和报告了酒精滥用和酒精中毒的行为和生物学表型。在当代实验文献中，已经付出了巨大的努力来发现遗传因素，这些因素最终在表型上被表达为对酒精滥用的倾向或敏感性。在人类和酗酒和酒精中毒的动物模型中，研究都大大提高了这个领域的知识，但是在许多情况下，很难在人类研究和动物研究的发现之间提出有意义的相似之处。该提案的重点是评估总体前提，即酒精的增强作用反映在表型反应中，部分由表型反应介导，并且这些表型包括行为（例如运动）和自主神经激活。在最近的研究中，我们研究了心率（HR）作为自主活动的指数，代表了对酒精给药和饮酒造成的一些独特概况（Bell等，2002）。提出的实验试图扩展这些发现并检验有关是否以及对酒精加强特性的行为和人力资源反应的程度以及至少部分从遗传性倾向到过多的酒精自我给药的程度。另一个目标是评估这些表型表征是否可以被证明是有用的，在评估对酒精加强功效的行为和神经生物学底物评估理论假设时的客观措施，这可以帮助药物治疗开发。为了实现这些目标，四个特定目标的实验将在有选择的育种大鼠中进行调查（1）乙醇给药的行为和HR剂量反应效应，（2）自由选择饮用中自我管理乙醇在自由选择饮用中的行为和HR激活效果响应，以及（4）直接进入大脑腹侧乙醇的行为和HR激活的作用，以便评估介导这些行为表型的潜在神经生物学底物。这些发现将有助于评估，扩展和验证所提出的措施作为过度寻求酒精行为的动物模型中的表型关联，并将在人类酒精中毒和那些对酒精滥用和酒精中毒的人中提供潜在的经验表型相似之处。