SELECTIVE BREEDING FOR ETHANOL SENSITIVITY

乙醇敏感性的选择性育种

• 批准号: 2894189
• 负责人: RICHARD A DEITRICH
• 金额: $ 27.59万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-18 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2894189
• 关键词: GABA receptor; alcoholism /alcohol abuse; animal breeding; dehydroepiandrosterone; ethanol; gene expression; genetic mapping; genetic susceptibility; glutamates; laboratory rat; quantitative trait loci

DESCRIPTION: (Adapted from the Investigator's Abstract) This proposal utilizes lines of rats that have been selected for differential initial sensitivity to ethanol. These lines will be used to discover which genes control the molecular mechanisms of action of ethanol in the brain. This information will be compared with similar data from mice and the results extrapolated to humans. Identification of genes responsible for the genetic risk of development of alcoholism is the ultimate goal of these studies. These rats, High Alcohol Sensitive, (HAS) and Low Alcohol Sensitive (LAS) and the control lines (CAS) have been selectively bred for 24 generations. The criteria for selection is "sleep time" and blood ethanol at awakening following a standard dose of ethanol. There is essentially no overlap between blood ethanol at awakening between the HAS and LAS lines. Replicate lines, started from separate stocks of the N/Nih heterogeneous stock of rats, are maintained. A Quantitative Trait Loci project is underway and depends upon this proposal for the phenotypic testing of parents, F1 and F2 animals from a cross of both outbred lines and inbred strains. In the current proposal, we undertake to more closely define the actions of ethanol at the GABA receptor and the role of glutamate in the actions of ethanol. We will also investigate very rapid acute tolerance, acute functional tolerance and rapid tolerance. We will investigate the actions of dehydroepiandrosterone and its sulfate derivative on the metabolism and actions of ethanol. Other neurosteroids have been found to have differential effects on ethanol responses in these lines of rats.

描述：（改编自研究者摘要）本提案 利用已经选择用于差异初始化的大鼠品系， 对乙醇敏感。 这些线将被用来发现哪些基因 控制乙醇在大脑中作用的分子机制。 这 这些信息将与来自小鼠的类似数据进行比较， 外推到人类身上 识别负责遗传的基因 酒精中毒发展的风险是这些研究的最终目标。 这些大鼠，高酒精敏感（HAS）和低酒精敏感（LAS） 对照系（CAS）已选育24代。 选择的标准是“睡眠时间”和觉醒时的血液乙醇 注射了标准剂量的乙醇 基本上没有重叠 HAS和LAS线之间的唤醒时血液乙醇之间的差异。 复制 线，从N/Nih异质股票的单独股票开始， 大鼠，保持。 一个数量性状基因座项目正在进行中，并取决于这一建议 对于亲本的表型测试，来自杂交的F1和F2动物 包括远交系和近交系。 在目前的提案中，我们承诺更严格地界定 乙醇对GABA受体的作用以及谷氨酸在 乙醇 我们还将研究非常快速的急性耐受性，急性 功能耐受性和快速耐受性。 我们会调查 脱氢表雄酮及其硫酸盐衍生物对代谢的影响， 乙醇的作用。 其他神经类固醇也被发现 对这些品系大鼠乙醇反应的不同影响。