Norman Haval, D'Souza Manoranjan S
Department of Pharmaceutical and Biomedical Sciences, The Raabe College of Pharmacy, Ohio Northern University, 525 S Main Street, Ada, OH, 45810, USA.
Psychopharmacology (Berl). 2017 May;234(9-10):1371-1394. doi: 10.1007/s00213-017-4582-0. Epub 2017 Mar 11.
Nicotine addiction continues to be a health challenge across the world. Despite several approved medications, smokers continue to relapse. Several human and animal studies have evaluated the role of the endogenous opioid system as a potential target for smoking cessation medications.
In this review, studies that have elucidated the role of the mu (MORs), delta (DORs), and kappa (KORs) opioid receptors in nicotine reward, nicotine withdrawal, and reinstatement of nicotine seeking will be discussed. Additionally, the review will discuss discrepancies in the literature and therapeutic potential of the endogenous opioid system, and suggest studies to address gaps in knowledge with respect to the role of the opioid receptors in nicotine dependence.
Data available till date suggest that blockade of the MORs and DORs decreased the rewarding effects of nicotine, while activation of the MORs and DORs decreased nicotine withdrawal-induced aversive effects. In contrast, activation of the KORs decreased the rewarding effects of nicotine, while blockade of the KORs decreased nicotine withdrawal-induced aversive effects. Interestingly, blockade of the MORs and KORs attenuated reinstatement of nicotine seeking. In humans, MOR antagonists have shown benefits in select subpopulations of smokers and further investigation is required to realize their full therapeutic potential.
Future work must assess the influence of polymorphisms in opioid receptor-linked genes in nicotine dependence, which will help in both identifying individuals vulnerable to nicotine addiction and the development of opioid-based smoking cessation medications. Overall, the endogenous opioid system continues to be a promising target for future smoking cessation medications.
尼古丁成瘾仍是全球范围内的一项健康挑战。尽管有几种已获批准的药物，但吸烟者仍会复吸。多项人体和动物研究评估了内源性阿片系统作为戒烟药物潜在靶点的作用。
在本综述中，将讨论阐明μ（MORs）、δ（DORs）和κ（KORs）阿片受体在尼古丁奖赏、尼古丁戒断及复吸中的作用的研究。此外，本综述还将讨论文献中的差异以及内源性阿片系统的治疗潜力，并提出相关研究以填补关于阿片受体在尼古丁依赖中作用的知识空白。
迄今为止可得的数据表明，阻断MORs和DORs可降低尼古丁的奖赏效应，而激活MORs和DORs可减轻尼古丁戒断引起的厌恶效应。相反，激活KORs可降低尼古丁的奖赏效应，而阻断KORs可减轻尼古丁戒断引起的厌恶效应。有趣的是，阻断MORs和KORs可减弱尼古丁觅求行为的复吸。在人类中，MOR拮抗剂已在部分吸烟者亚群中显示出益处，需要进一步研究以充分发挥其治疗潜力。
未来的工作必须评估阿片受体相关基因多态性对尼古丁依赖的影响，这将有助于识别易患尼古丁成瘾的个体以及开发基于阿片类的戒烟药物。总体而言，内源性阿片系统仍是未来戒烟药物颇具前景的靶点。
