Role of Orexin in Morphine Dependence and Withdrawal

描述(由申请人提供)：阿片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以及消极地强化和维持吸毒行为而导致复发。因此，要完全了解阿片成瘾，就需要彻底了解阿片戒断的神经机制。这项拟议的研究旨在调查新发现的丘脑下部神经肽-食欲素在阿片类药物沉淀戒断中的作用。这项研究还将调查急性吗啡对下丘脑食欲素能神经元的即刻影响和长期给药的影响。此外，通过使用CFOS免疫组织化学、顺行和逆行追踪技术以及针对Mu-阿片受体的腺相关病毒，这些研究将探索下丘脑和中皮质边缘通路上已知参与吗啡依赖和戒断的大脑区域之间的直接和间接神经网络。 公共卫生相关性：阿片成瘾仍然是我们社会的一个严重的健康问题，开发阿片成瘾的药物治疗方法需要了解药物滥用背后的神经生物学。食欲素系统可能是药物成瘾的重要组成部分，为了开发新的成瘾治疗方法，必须了解食欲素与药物的相互作用。

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.