Neuronal Basis of Control of Alcohol Consumption

控制酒精消耗的神经元基础

• 批准号: 6653760
• 负责人: HILARY J LITTLE
• 金额: $ 16.88万
• 依托单位: U OF L ST. GEORGE'S HOSPITAL MEDICAL SCH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6653760
• 关键词: adrenalectomy; alcoholic beverage consumption; autoradiography; cholecystokinin; corticosterone; corticotropin releasing factor; hormone receptor; hormone regulation /control mechanism; hypothalamic pituitary adrenal axis; laboratory mouse; neurochemistry; neuropharmacology; neuroregulation; protein transport; receptor expression; stress

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.

描述（由申请人提供）：酒精依赖和过量饮酒 消费造成重大健康问题和成本，两者都是直接的 和间接的。人类生活事件研究表明，压力经历会导致 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 大脑中导致酒精增加的神经元活动 压力经历引起的消费。具体目标是 确定C57小鼠饮酒量增加的机制 反复承受轻微压力。 C57菌株是“高度酒精 更喜欢“老鼠，但这个实验室已经表明，其中许多老鼠的基因水平较低， 而不是对酒精的高度偏爱，并且当 小鼠反复经历轻度压力。假设为 经检验，饮酒量增加是由于长时间 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以及 与饮酒量增加平行的受体。结果， 以及关于选择性行为影响的行为研究的结果 作用于酒精摄入量的药物，将提供详细信息 压力对这些系统的影响机制及其与 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的饮酒量持续增加 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可以通过药物来预防 作用于胆囊收缩素受体。结果将提供进一步的见解 研究这些系统如何参与酒精消费的控制和意愿 为开发新的治疗策略奠定基础。