The Alcohol Deprivation Effect and Locomotor Sensitizat*

描述(由申请人提供)： 这个应用程序中所追求的假设是，有共同的 重复产生两种效应的行为和生理机制 酒精体验：酒精剥夺效应，以及对 酒精的运动刺激作用。这项建议旨在更好地 了解大脑中发生的变化，特别强调 慢性酒精暴露所致的杏仁核延长，以改善 了解过度饮酒可能会导致人类的哪些变化 酒精中毒1运动敏感化和酒精剥夺效应 已经被认为是人类对药物依赖和/或渴望的模型。 该项目将使用选择性培育的高(HAP)和低(LAP)酒精 更喜欢老鼠，因为它们能很好地控制环境和遗传 因素，也因为HAP小鼠表现出大量自由选择的饮酒。 这项提议的目标1是确定反复饮酒是否 而剥夺HAP和LAP小鼠导致发育增加 喝酒。这种结果被称为反复酒精剥夺效应，或者 雷德。这种行为模式的发展具有遗传特征 MICE将构成一个有用的工具，以更好地了解 人类酗酒者的旧病复发和酗酒。目标2将评估是否 RADE程序导致对运动的敏感性的长期增加 酒精的刺激作用，提示运动敏感化。 此外，还将进行实验，以评估注射 酒精足以引起运动敏感化，产生类似Rade的反应 酒精摄入量增加。这些研究试图显示出一个共同点 Rade和运动敏化的原因。目标3将决定是否 注射足以引起HAP小鼠运动敏感化的酒精 引起HAP和LAP小鼠延长的杏仁核的变化，通过 即刻早期基因c-Fos的诱导。AIM 4评估是否类似 延长的杏仁核的变化是由Rade程序引起的， 运动敏化过程，提示了一种共同的神经机制 这两种行为模式。具体目标5将确定确切的类型 的神经元表现出c-Fos活性，这是敏化和辐射的结果，通过 针对特定神经递质合成的免疫细胞化学 小路。这些实验的结果将使我们更好地理解 导致过量饮酒的神经适应机制 酒精暴露。

DESCRIPTION (provided by applicant): The hypothesis being pursued in this application is that there are common behavioral and physiological mechanisms involved in two effects of repeated alcohol experience: the alcohol deprivation effect, and sensitization to the locomotor stimulating effects of alcohol. This proposal seeks to better understand changes which occur in the brain, with a special emphasis on the extended amygdala, as a result of chronic alcohol exposure, to better understand what changes might be caused by excessive drinking in human alcoholics.1 Both locomotor sensitization and the alcohol deprivation effect have been suggested as models of drug dependency and / or craving in humans. This project will use selectively bred High- (HAP) and Low- (LAP alcohol preferring mice, because they offer good control of environmental and genetic factors, and because HAP mice show substantial free-choice alcohol drinking. Aim 1 of this proposal is to determine whether repeated periods of alcohol access and deprivation in HAP and LAP mice leads to the development of increased drinking. This outcome is known as a repeated alcohol deprivation effect, or RADE. The development of this behavioral model in genetically characterized mice will comprise a useful tool for better understanding the causes of relapse and binge drinking in human alcoholics. Aim 2 will assess whether the RADE procedure results in long-term increases in sensitivity to the locomotor stimulating effects of alcohol, suggestive of locomotor sensitization. Additionally, experiments will be conducted assessing whether injections of alcohol sufficient to cause locomotor sensitization, induce RADE-like increases in alcohol intake. These studies seek to show a commonality in causes of the RADE and locomotor sensitization. Aim 3 will determine whether injections of alcohol sufficient to cause locomotor sensitization in HAP mice cause changes in the extended amygdala of HAP and LAP mice, as measured by induction of the immediate early gene, c-Fos. Aim 4 assesses whether similar changes in the extended amygdala are caused by the RADE procedure as by the locomotor sensitization procedure, suggesting a common neural mechanism for both these behavioral models. Specific Aim 5 will determine exactly what types of neurons show c-Fos activity as a result of sensitization and the RADE, by using immunocytochemistry aimed at specific neurotransmitter synthetic pathways. The results of these experiments will yield greater understanding of neuroadaptive mechanisms which cause excessive alcohol intake following alcohol exposure.