Neurobiol mechanism/acupuncture therapy/alcoholism

神经生物学机制/针灸疗法/酗酒

• 批准号: 6725907
• 负责人: JIANG-HONG YE
• 金额: $ 19.44万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6725907
• 关键词: acupuncture /acupressure; alcoholism /alcohol abuse therapy; behavior test; behavioral /social science research tag; brain cell; dopamine receptor; drug withdrawal; electrophysiology; ethanol; laboratory rat; membrane channels; neurobiology; neurons; nonhuman therapy evaluation; organ culture; relapse /recurrence; tegmentum; voltage /patch clamp

DESCRIPTION (provided by applicant): Alcohol abuse and alcoholism pose serious social and economic problems in the United States and around the world. Despite the increasing number of pharmacotherapies for alcoholism, current treatments have limited success and high rates of relapse. Although acupuncture has shown promising results in alleviating alcohol craving, the mechanism causing this effect remains unclear. Our long-range goal is to understand the neurobiological principles underlying acupuncture therapy for alcoholism. The objective of this proposal is to identify the changes induced by alcohol withdrawal and by acupuncture in rat dopamine neurons of the ventral tegmental area (VTA), a reward center of drug abuse. The central hypothesis is that acupuncture reverses or attenuates the reduction in excitability of dopamine neurons induced by the withdrawal of chronic ethanol administration and thus restores "normal" function of the dopamine system The changes caused by acupuncture can be detected in brain slices. We plan to test our hypothesis and accomplish the objective of this application by pursuing the following two Specific Aims: 1. Identify effects of ethanol withdrawal on dopamine neurons in brain slices. 2. Identify effects of acupuncture on alterations induced by ethanol withdrawals. Research design and methods: To achieve these aims, acupuncture/sham acupuncture will be given to rats withdrawn from chronic alcohol administration. While behavioral responses to withdrawal will be examined in vivo, the neuronal activities will be examined on VTA brain slices, using patch clamp techniques. The proposed work is innovative, because it will use proven modern techniques to elucidate the mechanisms of both acupuncture and its use in treating alcohol addiction. This approach is expected to yield the following outcomes: it will identify the effects of ethanol withdrawal on dopamine neurons in brain slices; optimize parameters of acupuncture to alter the neuronal responses induced by ethanol withdrawal, and elucidate changes induced by acupuncture in dopamine neurons of rats withdrawn from chronic ethanol administration. This new knowledge will have a major impact on our understanding of how acupuncture works. The application of this knowledge is expected to improve the effectiveness of acupuncture treatment in alcohol addiction.

描述（由申请人提供）：酗酒和酗酒在美国和世界各地造成严重的社会和经济问题。尽管治疗酒精中毒的药物疗法越来越多，但目前的治疗方法效果有限且复发率很高。尽管针灸在缓解酒精渴望方面显示出良好的效果，但造成这种效果的机制仍不清楚。我们的长期目标是了解针灸治疗酒精中毒的神经生物学原理。该提案的目的是确定酒精戒断和针灸对大鼠腹侧被盖区（VTA）多巴胺神经元（药物滥用奖励中心）引起的变化。中心假设是，针灸可以逆转或减弱因长期服用乙醇而引起的多巴胺神经元兴奋性降低，从而恢复多巴胺系统的“正常”功能。针灸引起的变化可以在脑切片中检测到。我们计划通过追求以下两个具体目标来检验我们的假设并实现本应用的目标： 1. 确定乙醇戒断对脑切片中多巴胺神经元的影响。 2. 确定针灸对乙醇戒断引起的变化的影响。研究设计和方法：为了实现这些目标，将对长期饮酒的大鼠进行针灸/假针灸。虽然将在体内检查对戒断的行为反应，但将使用膜片钳技术在 VTA 脑切片上检查神经元活动。拟议的工作具有创新性，因为它将使用经过验证的现代技术来阐明针灸及其治疗酒精成瘾的机制。这种方法预计将产生以下结果：它将确定乙醇戒断对脑切片中多巴胺神经元的影响；优化针灸参数以改变乙醇戒断引起的神经元反应，并阐明针灸对长期乙醇给药戒断的大鼠多巴胺神经元引起的变化。这些新知识将对我们对针灸原理的理解产生重大影响。这些知识的应用有望提高针灸治疗酒瘾的有效性。