Douglas Mental Health Institute, Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
Douglas Mental Health Institute, Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
Biol Psychiatry. 2020 Jan 1;87(1):54-63. doi: 10.1016/j.biopsych.2019.07.027. Epub 2019 Aug 6.
Opioid use disorder (OUD) is characterized by the development of a negative emotional state that develops after a history of long-term exposure to opioids. OUD represents a true challenge for treatment and relapse prevention. Human research has amply documented emotional disruption in individuals with an opioid substance use disorder, at both behavioral and brain activity levels; however, brain mechanisms underlying this particular facet of OUD are only partially understood. Animal research has been instrumental in elucidating genes and circuits that adapt to long-term opioid use or are modified by acute withdrawal, but research on long-term consequences of opioid exposure and their relevance to the negative affect of OUD remains scarce. In this article, we review the literature with a focus on two questions: 1) Do we have behavioral models in rodents, and what do they tell us? and 2) What do we know about the neuronal populations involved? Behavioral rodent models have successfully recapitulated behavioral signs of the OUD-related negative affect, and several neurotransmitter systems were identified (i.e., serotonin, dynorphin, corticotropin-releasing factor, oxytocin). Circuit mechanisms driving the negative mood of prolonged abstinence likely involve the 5 main reward-aversion brain centers (i.e., nucleus accumbens, bed nucleus of the stria terminalis, amygdala, habenula, and raphe nucleus), all of which express mu opioid receptors and directly respond to opioids. Future work will identify the nature of these mu opioid receptor-expressing neurons throughout reward-aversion networks, characterize their adapted phenotype in opioid abstinent animals, and hopefully position these primary events in the broader picture of mu opioid receptor-associated brain aversion networks.
阿片类药物使用障碍（OUD）的特征是在长期暴露于阿片类药物后会出现消极情绪状态。OUD 代表着治疗和预防复发的真正挑战。人类研究充分证明了阿片类物质使用障碍个体在行为和大脑活动水平上的情绪障碍；然而，OUD 这一特定方面的大脑机制仅部分得到理解。动物研究对于阐明适应长期阿片类药物使用或被急性戒断改变的基因和回路起到了重要作用，但关于阿片类药物暴露的长期后果及其与 OUD 的消极影响的相关性的研究仍然很少。在本文中，我们重点关注两个问题来回顾文献：1）我们是否有啮齿动物的行为模型，它们告诉了我们什么？2）我们对涉及的神经元群体了解多少？行为学啮齿动物模型成功地再现了与 OUD 相关的负性情绪的行为迹象，并且已经确定了几种神经递质系统（即，5-羟色胺、强啡肽、促肾上腺皮质释放因子、催产素）。驱动长期戒断的负面情绪的回路机制可能涉及 5 个主要的奖励-厌恶大脑中枢（即伏隔核、终纹床核、杏仁核、缰核和中缝核），所有这些都表达μ阿片受体并直接对阿片类药物产生反应。未来的工作将确定这些在奖励-厌恶网络中表达μ阿片受体的神经元的性质，描述在阿片类药物戒断动物中它们适应的表型，并希望将这些主要事件置于μ阿片受体相关的大脑厌恶网络的更广泛图景中。
