RAT RESEARCH COMPONENT

大鼠研究部分

• 批准号: 6097677
• 负责人: JAMES M MURPHY
• 金额: $ 21.25万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6097677
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; anxiety; attention; autonomic nervous system; behavioral genetics; behavioral habituation /sensitization; choice; disease /disorder model; dorsal raphe nucleus; drug interactions; drug tolerance; electrophysiology; ethology; gender difference; genetic susceptibility; laboratory rat; microdialysis; neurobiology; open field behavior; personality; phenotype; preference; psychological tests; reinforcer; serotonin; statistics /biometry

The majority of people who drink alcohol drink moderate amounts without serious consequences, but for a subset of individuals, drinking becomes excessive, leading to serious medical, social and legal consequences. The medical consequences alone may reduce expected life span by as much as 20 years; the social and legal consequences, including accidents, conflict with family and friends, job loss and arrest, severely decrease the quality of that shortened life. Recently, it has been recognized that individual differences in liability for alcohol abuse and alcoholism are associated with inherited personality traits. In particular, two patterns have been identified, 1) the disinhibited personality in which alcoholism accompanies high novelty-seeking, risk-taking, and indifference to social rewards and 2) the anxious personality, in which alcohol serves to reduce anxiety. In the present proposal, rats genetically selected for high or low levels of voluntary consumption of alcohol will be tested in models of disinhibition and anxiety to identify the precise neurobiological mechanisms that link each of these behaviors with alcohol drinking. Project 1 combines behavioral and physiological measures to assess the relationship between responses to novelty, attention, anxiety and anticipation to alcohol drinking. In project 2, behavioral and neurobiological techniques are combined to assess differences in brain arousal and inhibitory systems in the genetically selected lines. Project 3 explores the role of the mesocorticolimbic dopamine system in responses to novelty and alcohol drinking. By developing a better understanding of the inherited influences alcohol drinking, the basic biological mechanisms that increase individual liability for alcoholism can be better understood, and targeted strategies for prevention and treatment developed.

大多数饮酒的人喝适量的酒， 严重的后果，但对于一个子集的人，饮酒成为 过量，导致严重的医疗、社会和法律的后果。 的 仅医疗后果就可能使预期寿命减少20 社会和法律的后果，包括事故、冲突 与家人和朋友，失业和逮捕，严重减少 这缩短的生命的质量。 最近，人们认识到， 酒精滥用和酒精中毒的个体差异是 与遗传的性格特征有关。 特别是，两种模式 已经确定，1）酗酒的不羁人格， 伴随着高度的新奇寻求，冒险，以及对社会的漠不关心。 奖励和2）焦虑的个性，其中酒精有助于减少 焦虑 在目前的建议中，老鼠的基因选择高或 低水平的自愿饮酒将在以下模型中进行测试： 去抑制和焦虑，以确定精确的神经生物学 将这些行为与饮酒联系起来的机制。 项目1结合了行为和生理措施，以评估 对新奇感、注意力、焦虑和 对饮酒的期待。 在项目2中， 结合神经生物学技术来评估大脑中 唤醒和抑制系统的基因选择线。项目 3探讨了中皮质边缘多巴胺系统在反应中的作用 新奇和酗酒的人通过更好地了解 遗传影响饮酒，基本的生物学机制 增加个人酗酒责任可能会更好 有针对性的预防和治疗战略 开发