CHRONIC ETHANOL, DOPAMINE ELECTROPHYSIOLOGY, AND CRAVING

慢性乙醇、多巴胺电生理学和渴望

• 批准号: 2000322
• 负责人: ROH-YU SHEN
• 金额: $ 10.14万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2000322
• 关键词: GABA receptor; NMDA receptors; alcoholism /alcohol abuse; brain electrical activity; brain metabolism; dopamine; drug addiction; drug withdrawal; electrodes; electrophysiology; laboratory rat; membrane activity; membrane potentials; neural transmission; neurochemistry; neurons; neuroregulation; neurotransmitter metabolism; receptor sensitivity; single cell analysis; stereotaxic techniques; tegmentum; voltage /patch clamp

Craving for ethanol is an important factor for high rate of relapse during abstinence. In order to develop effective pharmacological treatment for alcoholism, it is important to understand neurological basis for craving. We have demonstrated a reduction in the spontaneous activity in dopaminergic (DA) neurons in the ventral tegmental area (area 10). This reduction may be the cause of decreased DA release and metabolism commonly observed during ethanol withdrawal period. Because activation of A10 DA system is proposed to mediate brain reward of addictive substances including ethanol, it is likely that this reduction in A10 DA neuron activity during ethanol withdrawal results in ethanol craving. The proposed studies in this application intent to use the electrophysiological approach to characterize the chronic ethanol's effects on the spontaneous activity of A10 DA neurons and the underlying mechanism. In order to understand the neuroadaptation process of A10 DA neurons to chronic ethanol treatment, experiments under Specific Aim l are designed to study the dose and time course effects of chronic ethanol treatment; The spontaneous activity of Al0 DA neurons will be examined during both the intoxication and initial withdrawal stages to provide information of corresponding changes to blood ethanol levels. Experiments under Specific Aim 2 will examine natural functional recovery of the spontaneous activity of A10 DA neurons during prolonged withdrawal period (abstinence). Results from our preliminary studies suggest that Al 0 DA neurons become inactivated because chronic ethanol treatment causes excessive depolarization which disrupts the action potential generation mechanisms. This hypothesis and the underlying cellular mechanisms will be studied with in vitro whole cell recording technique. The results obtained from this proposal will better our understanding in chronic ethanol's effects on A10 DA systems. Furthermore. the electrophysiological approach employed may be validated as a experimental model to explore possible therapeutic agents to alleviate craving for ethanol.

对酒精的渴求是高复发率的重要因素