ALCOHOL WITHDRAWAL IN RAT LINES SELECTED FOR PREFERENCE

描述：（改编自研究者摘要） 许多先前的工作与啮齿动物系选择性繁殖的差异， 酒精的摄入集中在酒精的强化作用上， 保持高度饮酒行为。该提案的重点是 酒精的厌恶效应也可能影响饮酒行为 在未接触酒精和有酒精经验的动物中。我们将确定 对酒精戒断（AW）敏感性的先天差异是否 与大鼠饮酒行为的遗传差异有关 选择性繁殖的酒精偏好和非偏好（P/NP和复制 HAD/LAD线）。虽然这些线已经在几个方面得到了很好的表征， 与酒精相关的特征被认为有助于加强 酒精的性质，这些线还没有被表征的方面， 对酒精的厌恶性敏感。初步数据 这表明，大鼠选择性地饲养酒精非偏好 (NP线）表明急性或慢性暴露于 比那些有选择性地为酒精而培育的同类更容易 偏好（P线）。在具体目标（SA）1中，我们将描述和比较 P/NP组大鼠对AW的敏感性以及酒精厌恶阈值 并在急性和慢性酒精处理后复制HAD/LAD系。在 SA 2，我们将确定是否过敏或耐受性发展到AW中， 在慢性酒精暴露后，使用程序 维持血液中酒精含量稳定的神经系统（酒精钳）。在SA 3中 我们将探讨AW严重程度与 在每一条选定的路线上饮酒。在SA 4中，我们将调查 阿片与下丘脑-垂体-肾上腺（HPA）的相互作用 调节AW严重程度的系统。我们假设，对 AW可能是一种遗传的特征，可以防止酗酒 选择性培育的低酒精偏好的啮齿动物品系的饮酒。 认识到必须表明， 表型（饮酒）和相关性状（对AW的敏感性）存在 在为相同表型选择的多于一个品系中，大多数的 拟议的研究将在三组大鼠品系中进行， 对于酒精偏好的差异（P/NP和复制的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).