Oleson Erik B, Cachope Roger, Fitoussi Aurelie, Cheer Joseph F
University of Maryland, School of Medicine, 20 Penn St., Baltimore, MD 21201, United States; University of Colorado Denver, P.O. Box 173364, Denver, CO 80217, United States.
University of Maryland, School of Medicine, 20 Penn St., Baltimore, MD 21201, United States.
Prog Neuropsychopharmacol Biol Psychiatry. 2014 Jul 3;52:17-23. doi: 10.1016/j.pnpbp.2013.07.019. Epub 2013 Aug 1.
Environmental and interoceptive cues are theorized to serve as 'signals' that motivate drug seeking and effects that may be augmented in the withdrawn state. Phasic dopamine release events are observed in the nucleus accumbens in response to such motivational salient stimuli and are thought to be necessary for drug-associated cues to trigger craving. We recently demonstrated how dopamine neurons encode stimuli conditioned to a negative event, as might occur during conditioned withdrawal, and stimuli predicting the avoidance of negative events, as might occur as an addict seeks out drugs to prevent withdrawal. In this review we first discuss how the subsecond dopamine release events might process conditioned withdrawal and drug seeking driven by negative reinforcement processes within the context of our dopamine data obtained during conditioned avoidance procedures. We next describe how the endocannabinoid system modulates phasic dopamine release events and how it might be harnessed to treat negative affective states in addiction. Specifically, we have demonstrated that endocannabinoids in the ventral tegmentum sculpt cue-induced accumbal surges in dopamine release and, therefore, may also be mobilized during drug withdrawal.
环境和内感受性线索被理论化为充当激发觅药行为的“信号”，以及在戒断状态下可能增强的效应。在伏隔核中观察到阶段性多巴胺释放事件，以响应此类动机性显著刺激，并且被认为是与药物相关的线索引发渴望所必需的。我们最近展示了多巴胺神经元如何编码与负面事件相关的条件刺激，这可能在条件性戒断期间发生，以及预测避免负面事件的刺激，这可能在成瘾者寻求药物以防止戒断时发生。在这篇综述中，我们首先讨论在条件性回避程序中获得的多巴胺数据背景下，亚秒级多巴胺释放事件可能如何处理由负强化过程驱动的条件性戒断和觅药行为。接下来，我们描述内源性大麻素系统如何调节阶段性多巴胺释放事件，以及如何利用它来治疗成瘾中的负面情绪状态。具体而言，我们已经证明腹侧被盖区的内源性大麻素塑造了线索诱导的伏隔核多巴胺释放激增，因此，在药物戒断期间也可能被调动起来。
