SELECTIVE BREEDING FOR ETHANOL SENSITIVITY

乙醇敏感性的选择性育种

• 批准号: 6168364
• 负责人: RICHARD A DEITRICH
• 金额: $ 28.42万
• 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/6168364
• 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）该提案 利用已选择用于差异初始的大鼠品系 对乙醇的敏感性。 这些细胞系将用于发现哪些基因 控制乙醇在大脑中作用的分子机制。 这 信息将与来自小鼠的类似数据进行比较，结果 推断到人类。 鉴定负责遗传的基因 酗酒的风险是这些研究的最终目标。 这些大鼠，高度酒精敏感 (HAS) 和低度酒精敏感 (LAS) 对照系（CAS）已选育24代。 选择的标准是“睡眠时间”和醒来时的血乙醇 按照标准剂量的乙醇。 本质上没有重叠 醒来时血液乙醇之间的 HAS 线和 LAS 线之间。 复制 线，从 N/Nih 异质库存的单独库存开始 老鼠，被维持。 数量性状基因座项目正在进行中，并取决于该提案 用于亲本、F1 和 F2 动物杂交的表型测试 远交系和近交系。 在当前的提案中，我们承诺更严格地定义 乙醇在 GABA 受体上的作用以及谷氨酸在以下作用中的作用 乙醇。 我们还将研究非常快速的急性耐受性、急性 功能耐受和快速耐受。 我们将调查这些行为 脱氢表雄酮及其硫酸盐衍生物对代谢的影响 乙醇的作用。 其他神经类固醇被发现具有 对这些大鼠系的乙醇反应有不同的影响。