阿片受体作用系统与抑郁症发病及干预研究进展

Progresses in relationship between opioid receptor system and depression and intervention strategies

抑郁症是一种常见且危害巨大、病因和发病机制尚未阐明的以抑郁情绪为主要表现的精神障碍。在治疗方面,药物抗抑郁治疗存在起效缓慢、疗效有限、不良反应严重和用药早期不能很好控制自杀倾向等问题。阐明抑郁症发病原因和神经生物学机制,发现更为理想的抗抑郁药物是本领域急需解决的重大科学问题。近年来,阿片受体作用系统与抑郁症的关系越来越引起人们的重视,已成为本领域的一个研究热点。抑郁症的核心症状包括正性体验减少、负性情绪增加和认知功能障碍,内源性阿片肽及阿片受体在抑郁症相关的脑区中表达。本文重点讨论了阿片受体作用系统如何调控中脑-皮质-边缘通路介导的动机及奖赏、以杏仁核为中心的边缘环路介导的恐惧及焦虑、前额叶皮质和海马介导的认知功能,进而在抑郁症的发病中发挥重要作用,并综述了阿片类药物抗抑郁作用的相关研究进展。对阿片系统参与抑郁症病理过程的全面理解,可能为治疗抑郁症提供新的策略和候选靶标。

Depression is one of the most prevalent psychiatric disorders,which causes serious harm.However,the etiology and pathogenesis of depression remain unclear.Predominant antidepressants cause several problems,such as slow onset of therapeutic efficacy,resistance to drug therapy,serious adverse effects and failure to control suicidal ideation during early administration.Therefore,it is urgent to illuminate the etiology and neurobiological mechanisms of depression and discover novel antidepressants.Recently,the relationship between the opioid receptor system and depression has attracted attention and become a hot topic.Core features of depression include diminished positive valence,increased negative emotions and cognitive impairment.Endogenous opioid peptides and receptors are abundant in the brain regions related to the pathological process of depression.This review focuses on how the opioid system potently modulates mesolimbic circuitry underlying motivation and reward processing,limbic circuitry underlying fear and anxiety responses,cortical and hippocampal circuitry underlying a variety of cognitive functions,as well as the anti-depressive actions of opioid medications.A better understanding of how the opioid system participates in the pathological processes may lead to novel treatment strategies and potential molecular targets in the treatment of depression.