Role of Orexin in Morphine Dependence and Withdrawal

描述（由申请人提供）：阿片类药物成瘾的一个主要问题是复发。戒毒后的戒断症状通过引发寻求毒品和消极地加强和维持吸毒而促成复吸。因此，一个完整的了解阿片类药物成瘾需要彻底了解阿片类药物戒断的神经机制。这项研究的目的是调查食欲素，新发现的下丘脑神经肽，在阿片类药物戒断过程中的作用。本研究亦将探讨急性吗啡对下丘脑食欲素能神经元的即时效应及慢性吗啡给药对下丘脑食欲素能神经元的长期效应。此外，通过使用cFos免疫组织化学，顺行和逆行追踪技术，以及靶向μ阿片受体的腺相关病毒，这些研究将探索下丘脑和大脑区域的食欲素能神经元之间的直接和间接的神经网络沿着中皮质边缘通路已知参与吗啡依赖和戒断。 公共卫生相关性：阿片类药物成瘾仍然是一个严重的健康问题，在我们的社会和阿片类药物成瘾的药物治疗的发展将需要了解药物滥用的神经生物学基础。食欲素系统可能是药物成瘾的一个组成部分，为了开发新的成瘾治疗方法，必须了解食欲素-药物相互作用。

DESCRIPTION (provided by applicant): A major problem in opiate addiction is relapse. Withdrawal symptoms following abstinence from a drug contribute to relapse by initiating drug-seeking and by negatively reinforcing and maintaining drug-taking. Thus, a complete understanding of opiate addiction requires a thorough understanding of the neural mechanisms underlying opiate withdrawal. The proposed research aims to investigate the role of orexins, newly discovered hypohalamic neuropeptides, in precipitated opioid withdrawal. This research will also investigate the immediate effects of acute morphine and the long term effects of chronic morphine administration on orexinergic hypothalamic neurons. Moreover, through the use of cFos immunohistochemistry, anterograde and retrograde tracing techniques, and adenoassociated viruses targeting mu-opioid receptors, these studies will explore the direct and indirect neural networks between orexinergic neurons of the hypothalamus and brain regions along the mesocorticolimbic pathway known to be involved in morphine dependence and withdrawal. PUBLIC HEALTH RELEVANCE: Opiate addiction remains a serious health problem in our society and the development of pharmacotherapeutic treatments for opiate addiction will require an understanding of the neurobiology underlying drug abuse. The orexin system may be an integral component underlying drug addiction and orexin-drug interactions must be understood for the development of new treatments for addiction.