Integrative Neuroscience Section, Integrative Neuroscience Research Branch, NIDA-IRP, NIH, Baltimore, MD 21224, USA.
Cell Mol Life Sci. 2012 Mar;69(6):857-96. doi: 10.1007/s00018-011-0844-x. Epub 2011 Oct 16.
The dynorphin/κ-opioid receptor system has been implicated in the pathogenesis and pathophysiology of several psychiatric disorders. In the present review, we present evidence indicating a key role for this system in modulating neurotransmission in brain circuits that subserve mood, motivation, and cognitive function. We overview the pharmacology, signaling, post-translational, post-transcriptional, transcriptional, epigenetic and cis regulation of the dynorphin/κ-opioid receptor system, and critically review functional neuroanatomical, neurochemical, and pharmacological evidence, suggesting that alterations in this system may contribute to affective disorders, drug addiction, and schizophrenia. We also overview the dynorphin/κ-opioid receptor system in the genetics of psychiatric disorders and discuss implications of the reviewed material for therapeutics development.
孤啡肽/κ 阿片受体系统与几种精神疾病的发病机制和病理生理学有关。在本综述中,我们提供了证据表明该系统在调节参与情绪、动机和认知功能的大脑回路中的神经递质传递方面发挥着关键作用。我们综述了孤啡肽/κ 阿片受体系统的药理学、信号转导、翻译后、转录后、转录、表观遗传和顺式调控,并批判性地回顾了功能神经解剖学、神经化学和药理学证据,表明该系统的改变可能与情感障碍、药物成瘾和精神分裂症有关。我们还综述了精神疾病遗传学中的孤啡肽/κ 阿片受体系统,并讨论了所综述材料对治疗开发的意义。