CORE--SCIENTIFIC/SELECTION FOR ALCOHOL-RELATED PHENOTYPES

核心——酒精相关表型的科学/选择

• 批准号: 5204207
• 负责人: V GENE ERWIN
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5204207
• 关键词: alcoholic beverage consumption; animal breeding; behavioral genetics; biological models; biomedical facility; drug tolerance; drug withdrawal; ethanol; genetic markers; genetic polymorphism; genetic strain; laboratory mouse; neurochemistry; polymerase chain reaction; restriction fragment length polymorphism

In animals a convincing body of literature has shown genetic influences on ethanol-related behaviors including measures of initial sensitivity, voluntary ethanol consumption (VEC), acute functional tolerance (AFT) and withdrawal severity (WS) following chronic ethanol exposure. The proposed studies will identify those genes and/or expression products which mediate genetic differences in VEC, AFT, and WS. Selective breeding procedures will be used to obtain ethanol-avoiding congenic strains of ethanol-preferring C57BL mice. Investigators will use these mice and RFLP and PCR methods to determine quantitative trait loci (QTL) for VEC and correlated behavioral effects of ethanol including locomotor activation and inhibition, and conditioned place-preference. Two other studies will obtain, by selective breeding from a genetically heterogeneous (HS) stock, replicate lines of mice which differ in AFT (HAFT1,2 and LAFT1,2) and in WS (HW1,2 and LW1,2). Specific neurochemical hypotheses for GABAergic, dopaminergic, serotonergic, and peptidergic mediation of these alcohol-related behaviors will be investigated. Identification of the genes and subsequent neuronal and neurochemical processes mediating individual differences in VEC, AFT, and WS will lead ultimately to improved methods of identifying individuals at risk for alcoholism and consequently will enhance methods of prevention and treatment of this major societal problem.

在动物中，大量令人信服的文献显示了遗传的影响 与乙醇相关的行为，包括初始敏感性测量， 自愿乙醇消耗（VEC）、急性功能耐受（AFT）和 慢性乙醇暴露后的戒断严重程度（WS）。 这 拟议的研究将鉴定这些基因和/或表达产物 介导 VEC、AFT 和 WS 的遗传差异。 选择性 育种程序将用于获得避免乙醇的同类品种 偏好乙醇的 C57BL 小鼠品系。 调查人员将使用这些 小鼠和 RFLP 和 PCR 方法确定数量性状基因座 (QTL) 用于 VEC 和乙醇的相关行为影响（包括运动） 激活和抑制，以及条件性位置偏好。 另外两个 研究将通过选择性育种获得 异质（HS）库存，AFT 不同的小鼠复制系 （HAFT1,2 和 LAFT1,2）和 WS（HW1,2 和 LW1,2）。 具体的 GABA 能、多巴胺能、血清素能和 这些与酒精相关的行为的肽能介导将是 调查了。 基因和后续神经元的鉴定 神经化学过程介导 VEC、AFT 和 WS 最终将改进识别个人的方法 有酗酒的风险，因此将加强酗酒的方法 防治这一重大社会问题。