Zhang Jia-Jia, Song Chang-Geng, Dai Ji-Min, Li Ling, Yang Xiang-Min, Chen Zhi-Nan
National Translational Science Center for Molecular Medicine & Department of Cell Biology The Fourth Military Medical University Xi'an China.
Department of Neurology Xijing Hospital The Fourth Military Medical University Xi'an China.
MedComm (2020). 2022 Jun 22;3(3):e148. doi: 10.1002/mco2.148. eCollection 2022 Sep.
Opioid abuse and addiction have become a global pandemic, posing tremendous health and social burdens. The rewarding effects and the occurrence of withdrawal symptoms are the two mainstays of opioid addiction. Mu-opioid receptors (MORs), a member of opioid receptors, play important roles in opioid addiction, mediating both the rewarding effects of opioids and opioid withdrawal syndrome (OWS). The underlying mechanism of MOR-mediated opioid rewarding effects and withdrawal syndrome is of vital importance to understand the nature of opioid addiction and also provides theoretical basis for targeting MORs to treat drug addiction. In this review, we first briefly introduce the basic concepts of MORs, including their structure, distribution in the nervous system, endogenous ligands, and functional characteristics. We focused on the brain circuitry and molecular mechanism of MORs-mediated opioid reward and withdrawal. The neuroanatomical and functional elements of the neural circuitry of the reward system underlying opioid addiction were thoroughly discussed, and the roles of MOR within the reward circuitry were also elaborated. Furthermore, we interrogated the roles of MORs in OWS, along with the structural basis and molecular adaptions of MORs-mediated withdrawal syndrome. Finally, current treatment strategies for opioid addiction targeting MORs were also presented.
阿片类药物滥用和成瘾已成为全球性的流行病，带来了巨大的健康和社会负担。奖赏效应和戒断症状的出现是阿片类药物成瘾的两大主要特征。μ-阿片受体（MORs）作为阿片受体家族的一员，在阿片类药物成瘾中发挥着重要作用，介导阿片类药物的奖赏效应和阿片戒断综合征（OWS）。MOR介导的阿片奖赏效应和戒断综合征的潜在机制对于理解阿片类药物成瘾的本质至关重要，也为以MOR为靶点治疗药物成瘾提供了理论依据。在本综述中，我们首先简要介绍MOR的基本概念，包括其结构、在神经系统中的分布、内源性配体和功能特性。我们重点关注MOR介导的阿片奖赏和戒断的脑环路及分子机制。深入讨论了阿片类药物成瘾背后奖赏系统神经环路的神经解剖学和功能要素，同时也阐述了MOR在奖赏环路中的作用。此外，我们探讨了MOR在OWS中的作用，以及MOR介导的戒断综合征的结构基础和分子适应性变化。最后，还介绍了目前针对MOR治疗阿片类药物成瘾的策略。
