ALCOHOL WITHDRAWAL IN RAT LINES SELECTED FOR PREFERENCE

描述：(改编自《调查者摘要》) 以前的许多工作都是针对啮齿动物品系的差异而选择性地培育出来的 酒精摄入量的重点是酒精对促进健康的强化作用 并保持高酒精饮酒行为。这项提案的重点是 酒精的厌恶效应也可能影响饮酒行为 在酗酒和酗酒的动物中都是如此。我们将决定 对酒精戒断(AW)的敏感性是否存在先天差异 与大鼠饮酒行为的遗传差异有关 有选择地为酒精偏好和非偏好繁殖(P/NP和复制 HAD/LAD行)。虽然这些线已经在几个方面得到了很好的描述 与酒精相关的特征被认为有助于增强 对于酒精的性质，这些线条还没有被表征为 对酒精令人厌恶的特性的敏感性。初步数据为 这表明大鼠是为了不喜欢酒精而有选择地饲养的 (NP系列)急性或慢性接触AW后AW严重程度更高的证据 给予一定剂量的酒精，而不是他们的同龄人选择性地为酒精而培养 偏好(P线)。在《特定目标》(SA)1中，我们将描述和比较 P/NP大鼠对AW的敏感性及酒精厌恶阈值 急性和慢性酒精处理后复制HAD/LAD细胞系。在……里面 Sa 2我们将确定是否对AW产生敏感化或耐受性 慢性酒精暴露后的每一条选定的线使用一个程序 维持稳定的血液酒精水平(“酒精夹”)。在SA 3中 我们将探讨AW严重性与发生 在每个选定的品系中，随后饮酒。在SA 4中，我们将调查 阿片类药物与下丘脑-垂体-肾上腺(HPA)的相互作用 调解AW严重程度的系统。我们假设，增加对 AW可能是一种遗传特征，当遗传时，有助于防止酗酒 在为低酒精偏好而选择性培育的啮齿动物品系中饮酒。 认识到证明两国关系的重要性 表型(饮酒)和相关性状(对AW的敏感性)存在 在为同一表型选择的多个品系中，大多数 拟议的研究将在三组选择性培育的大鼠品系中进行 酒精偏好的差异(P/NP和复制HAD/LAD系)。

DESCRIPTION: (Adapted from the Investigator's Abstract) Much of the prior work with rodent lines selectively bred for differences in alcohol intake has focused on the reinforcing effects of alcohol that promote and maintain high alcohol drinking behavior. This proposal focuses on the aversive effects of alcohol that may also influence alcohol drinking behavior in both alcohol-naive and alcohol-experienced animals. We will determine whether innate differences in sensitivity to alcohol withdrawal (AW) are associated with genetic differences in alcohol drinking behavior in rat lines selectively bred for alcohol preference and -nonpreference (P/NP and replicate HAD/LAD lines). While these lines have been well characterized on several alcohol-related traits that are thought to contribute to the reinforcing properties of alcohol, the lines have not been characterized in terms of sensitivity to the aversive properties of alcohol. Preliminary data are presented which suggest that rats selectively bred for alcohol nonpreference (NP line) evidence greater AW severity after acute or chronic exposure to a given dose of alcohol than do their counterparts selectively bred for alcohol preference (P line). In Specific Aim (SA) 1 we will characterize and compare sensitivity to AW, as well as alcohol aversion threshold, in rats of the P/NP and replicate HAD/LAD lines following acute and chronic alcohol treatment. In SA 2 we will determine whether sensitization or tolerance develops to AW in each of the selected lines following chronic alcohol exposure using a procedure that maintains steady state blood alcohol levels (the "alcohol clamp"). In SA 3 we will explore the relationship between AW severity and probability of subsequent alcohol drinking in each selected line. In SA 4 we will investigate the interaction between the opioid and hypothalamic-pituitary- adrenal (HPA) systems in mediating AW severity. We hypothesize that increased sensitivity to AW may be a trait that, when inherited, serves to protect against high alcohol drinking in rodent lines selectively bred for low alcohol preference. Recognizing the importance of demonstrating that the relationship between the phenotype (alcohol drinking) and the related-trait (sensitivity to AW) exists in more than one line selected for the same phenotype, the majority of the proposed studies will be conducted in three sets of rat lines selectively bred for differences in alcohol preference (P/NP and replicate HAD/LAD lines).