Role of Orexin in Morphine Dependence and Withdrawal

描述（由申请人提供）：鸦片成瘾的一个主要问题是复发。戒断后出现的戒断症状会引发药物寻求，并负性地加强和维持药物服用，从而导致复发。因此，对阿片类药物成瘾的全面理解需要对阿片类药物戒断背后的神经机制有透彻的了解。本研究旨在探讨新发现的下丘脑神经肽食欲素在阿片类药物沉淀戒断中的作用。本研究还将探讨急性吗啡给药对食欲能下丘脑神经元的即时影响和长期影响。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μ -阿片受体的腺相关病毒，这些研究将探索下丘脑的食欲能神经元和大脑区域之间的直接和间接神经网络，这些神经网络沿着中皮质边缘通路已知参与吗啡依赖和戒断。

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.