SELECTIVE BREEDING FOR ETHANOL SENSITIVITY

描述：(改编自《调查员摘要》)本提案 利用已选择用于区分初始的大鼠品系 对乙醇的敏感性。这些品系将被用来发现哪些基因 控制酒精在大脑中的分子作用机制。这 信息将与来自MICE的类似数据和结果进行比较 推论到人类身上。遗传相关基因的鉴定 发展成酒精中毒的风险是这些研究的最终目标。 这些大鼠对酒精高度敏感(HAS)和低酒精敏感(LAS) 对照系(CAS)已选育了24代。 选择的标准是“睡眠时间”和醒来时的血液酒精。 在标准剂量的乙醇之后。基本上没有重叠 在HAS和LAS线之间觉醒时血液中的乙醇。复制 行，从N/NIH异质库存的单独库存开始 老鼠，都被养着。 一个数量性状基因座项目正在进行中，并依赖于这一提议 用于亲本、F1和F2动物的表型测试 既有近交系，也有近交系。 在目前的提案中，我们承诺更严格地界定 乙醇作用于GABA受体及谷氨酸在谷氨酸作用中的作用 乙醇。我们还将调查非常迅速的急性耐受性，急性 功能耐受和快速耐受。我们将对这些行为进行调查 脱氢表雄酮及其硫酸盐衍生物对机体代谢的影响 乙醇的作用。其他神经类固醇已被发现具有 对这些品系的大鼠的酒精反应的不同影响。

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.