Tales from the dark side: do neuromodulators of drug withdrawal require changes in endocannabinoid tone?
Tales from the dark side: do neuromodulators of drug withdrawal require changes in endocannabinoid tone?
复制标题
黑暗面的故事：戒断神经调节剂是否需要改变内源性大麻素的基调？
DOI：
10.1016/j.pnpbp.2013.07.019
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发表时间：
2014
影响因子：
5.6
通讯作者：
Cheer,JosephF
中科院分区：
文献类型：
--
作者：
Oleson,ErikB;Cachope,Roger;Fitoussi,Aurelie;Cheer,JosephF
环境和内感受性线索被理论化为“信号”，激励药物寻求和效果，可能会增加在撤回状态。在延髓核中观察到相性多巴胺释放事件，以响应这种动机性显著刺激，并且被认为是药物相关线索触发渴望所必需的。我们最近展示了多巴胺神经元如何编码条件性负面事件的刺激，就像条件性戒断过程中可能发生的那样，以及预测避免负面事件的刺激，就像成瘾者寻找药物以防止戒断一样。在这篇综述中，我们首先讨论如何亚秒多巴胺释放事件可能会处理条件性戒断和药物寻求驱动的负强化过程的背景下，我们的多巴胺数据在条件性回避程序。接下来，我们将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感状态。具体来说，我们已经证明，内源性大麻素在腹侧被盖造型线索诱导的多巴胺释放的脑电波浪涌，因此，也可能在药物戒断过程中动员。
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cues are theorized to serve as ‘signals’ that motivate drug seeking and effects that may be augmented in the withdrawn state.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.