Neuronal Basis of Control of Alcohol Consumption

描述（由申请人提供）：酒精依赖和过量饮酒

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.