The Alcohol Deprivation Effect and Locomotor Sensitizat*

描述（由申请人提供）： 在本申请中所追求的假设是， 行为和生理机制参与的两种影响的重复 酒精经验：酒精剥夺效应，以及对酒精的敏感性。 酒精的运动刺激作用。该提案旨在更好地 了解大脑中发生的变化，特别强调 由于长期酒精暴露，杏仁核延长， 了解过量饮酒可能会导致人类的哪些变化 1运动敏化和酒精剥夺效应 已经被建议作为人类药物依赖和/或渴望的模型。 该项目将使用选择性培育的高（HAP）和低（HAP）酒精 更喜欢老鼠，因为它们可以很好地控制环境和遗传 因为HAP小鼠表现出大量的自由选择饮酒。 该提案的目的1是确定是否重复饮酒 HAP和HAP小鼠的剥夺导致了增加的 喝酒这种结果被称为反复酒精剥夺效应，或 拉德。这种行为模式的发展， 老鼠将是一个有用的工具，可以更好地了解 酗酒者的复发和酗酒。目标2将评估 拉德程序导致对运动的敏感性长期增加 酒精的刺激作用，提示自发敏化。 此外，将进行实验，评估注射 酒精足以引起运动致敏，诱导RADE样 酒精摄入量增加。这些研究试图表明一个共同点， 拉德和运动致敏的原因。目标3将决定是否 注射足以引起HAP小鼠自发致敏的酒精 引起HAP和HAP小鼠杏仁核延长的变化， 立即早期基因c-Fos的诱导。目标4评估是否类似 延伸杏仁核的变化是由拉德程序引起的， 运动敏化程序，这表明一个共同的神经机制， 这两种行为模式。具体目标5将确定哪些类型 的神经元显示c-Fos活性作为致敏和拉德的结果， 利用免疫细胞化学技术， 途径。这些实验的结果将使我们更好地了解 神经适应机制导致过量酒精摄入， 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.