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)：几十年来，酒精滥用和酒精中毒的行为和生物学表型已经在文献中被描述、调查和报告。在当代实验文献中，已经有相当大的努力来发现遗传因素，这些因素最终表现为酗酒的倾向或易感性。这一领域的知识通过对人类和酒精滥用和酒精中毒的动物模型的研究得到了相当大的进步，但在许多情况下，很难将人类研究的结果与动物研究的结果进行有意义的比较。这项建议侧重于对酒精增强效应反映在表型反应中并部分由表型反应介导的总体前提的评估，以及这些表型包括行为(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)作为自主神经活动的指标，它代表了酒精摄入和饮酒导致的一些独特的特征(Bell等人，2002年)。拟议中的实验试图扩展这些发现，并测试关于行为和HR对酒精强化特性的反应是否以及在多大程度上至少部分地导致遗传易感性和过度饮酒自我管理的假设。另一个目标是评估这些表型特征是否可以被证明是有用的、客观的衡量标准，以评估关于酒精增强疗效的行为和神经生物学底物的理论假设，这可能有助于药物治疗的开发。为了实现这些目标，四个特定目标的实验将在选择性繁殖的大鼠中调查(1)酒精注射的行为和HR剂量-反应效应，(2)自由选择饮酒中自我给予乙醇的行为和HR激活效应，(3)以操作型范式设计的自我给予乙醇的行为和HR激活效应，该范式旨在评估预期、消退和反应恢复时期，以及(4)脑内自我给予乙醇直接进入大脑腹侧被盖区的行为和HR激活效应，以提供对调节这些行为表型的潜在神经生物底物的评估。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饮酒行为动物模型中的表型关联，并将为人类酗酒者和那些容易酗酒和酗酒的人的特征表型提供潜在的经验相似之处。