Neuronal Basis of Control of Alcohol Consumption

描述（由申请人提供）：酒精依赖和过量酒精 消费是造成重大健康问题和费用的直接原因， 间接的。人类生活事件研究表明， 与随后的过量饮酒有关，但知之甚少 这是如何发生的。该项目的目的是确定 大脑中的神经元活动导致酒精含量增加 压力体验导致的消耗。具体目标是 确定C57小鼠饮酒量增加的机制 通过反复暴露于轻微的压力。C57菌株是“高度酒精 但这个实验室已经表明，他们中的许多人有一个低， 而不是对酒精的高度偏好，并且当 将小鼠反复暴露于轻度压力体验。假设， 可以测试的是，增加酒精消费是由于长期 中枢神经系统胆囊收缩素传递的改变 和/或应激激素的释放或作用。实验将 确定激素和神经递质浓度的变化， 这些受体与酒精消耗量的增加相平行。结果， 以及行为研究中关于选择性地 代理药物对酒精摄入量，将提供详细的信息， 应力对这些系统的影响的机制和关系， 控制酒精摄入。该模型的主要优点是， 轻微的压力会导致小鼠饮酒量的持续增加， 基因相似，即使没有酒精也能看到效果 在压力和酒精摄入量增加的情况下， 作用于胆囊收缩素受体。结果将提供进一步的见解 这些系统如何参与控制酒精消费， 为开发新的治疗策略奠定了基础。

DESCRIPTION (provided by applicant): Alcohol dependence and excess alcohol consumption are responsible for major health problems and costs, both direct and indirect. Human life event studies have shown stressful experiences are associated with subsequent excessive alcohol consumption, but little is known of how this occurs. The aim of this project is to identify the alterations in neuronal activity in the brain responsible for the increased alcohol consumption caused by stressful experience. The specific objective is to determine the mechanism of the increased alcohol consumption of C57 mice caused by repeated exposure to minor stress. The C57 strain are "high alcohol preferring" mice, but this laboratory has shown that many of them have a low, rather than a high, preference for alcohol and that this is increased when the mice are repeatedly exposed to mildly stressful experiences. The hypothesis to be tested is that the increased alcohol consumption is due to prolonged alterations in cholecystokinin transmission in the central nervous system and/or in the release or actions of stress hormones. The experiments will determine the changes in hormone and neurotransmitter concentrations and receptors that parallel the increase in alcohol consumption. The results, together with those from behavioural studies on the effects of selectively acting drugs on the alcohol intake, will provide detailed information on the mechanism of the effects of stress on these systems and the relationship to the control of alcohol intake. The model has the major advantages that relatively minor stress causes consistent increase in alcohol drinking in mice that are genetically similar, the effect is seen even when alcohol is not available during the stress and the increased alcohol intake is prevented by a drug acting on cholecystokinin receptors. The results will provide further insight into how these systems are involved in control of alcohol consumption and will form a basis for the development of novel therapeutic strategies.