Neuronal Basis of Control of Alcohol Consumption

描述(申请人提供)：酒精依赖和过量饮酒 消费是造成重大健康问题和成本的主要原因，两者都是直接的 而且是间接的。人类生活事件研究表明，压力经历是 与随后的过度饮酒有关，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与酒精含量增加有关 由紧张的经历引起的消费。具体目标是 C57小鼠饮酒量增加的机制探讨 通过反复暴露在轻微的压力下。C57菌株的酒精含量很高。 更喜欢“老鼠”，但这个实验室表明，它们中的许多都有低血压， 而不是对酒精的高度偏好，而且当 小鼠被反复暴露在轻度压力的经历中。假设是为了 被测试的是，酒精消耗量的增加是由于长时间的 中枢神经系统中缩胆囊素传递的改变 和/或压力荷尔蒙的释放或作用。这些实验将会 测定荷尔蒙和神经递质浓度的变化 与酒精消耗量增加同步的受体。结果是， 以及来自行为研究的关于有选择性地 关于酒精摄入量的代理药物，将提供详细的信息 应激对这些系统的影响机制及其与细胞周期的关系 控制酒精摄入量。该模型的主要优点是相对 轻微的压力会导致小鼠饮酒量的持续增加 在基因上类似，即使在没有酒精的情况下也能看到这种影响 在压力和酒精摄入量增加期间，一种药物可以防止 作用于缩胆囊素受体。研究结果将提供进一步的洞察力 这些系统是如何参与控制酒精消费的，并将 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.