Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Psychiatry, Translational Neuroscience Program, University of Pittsburgh, Pittsburgh, PA, USA.
FEBS J. 2021 Mar;288(5):1462-1474. doi: 10.1111/febs.15496. Epub 2020 Aug 11.
Projections of ventral tegmental area dopamine (DA) neurons to the medial shell of the nucleus accumbens have been increasingly implicated as integral to the behavioral and physiological changes involved in the development of substance use disorders (SUDs). Recently, many of these nucleus accumbens-projecting DA neurons were found to also release the neurotransmitter glutamate. This glutamate co-release from DA neurons is critical in mediating the effect of drugs of abuse on addiction-related behaviors. Potential mechanisms underlying the role(s) of dopamine/glutamate co-release in contributing to SUDs are unclear. Nevertheless, an important clue may relate to glutamate's ability to potentiate loading of DA into synaptic vesicles within terminals in the nucleus accumbens in response to drug-induced elevations in neuronal activity, enabling a more robust release of DA after stimulation. Here, we summarize how drugs of abuse, particularly cocaine, opioids, and alcohol, alter DA release in the nucleus accumbens medial shell, examine the potential role of DA/glutamate co-release in mediating these effects, and discuss future directions for further investigating these mechanisms.
腹侧被盖区多巴胺（DA）神经元向伏隔核内侧壳的投射，越来越多地被认为是参与物质使用障碍（SUD）发展的行为和生理变化的组成部分。最近，许多这些投射到伏隔核的 DA 神经元也被发现释放神经递质谷氨酸。DA 神经元的这种谷氨酸共同释放对于调节滥用药物对成瘾相关行为的影响至关重要。多巴胺/谷氨酸共同释放在导致 SUD 中的作用的潜在机制尚不清楚。然而，一个重要的线索可能与谷氨酸的能力有关，即在药物引起的神经元活动增加时，谷氨酸能够增强伏隔核内末梢中 DA 进入突触小泡的装载，从而在刺激后释放更多的 DA。在这里，我们总结了滥用药物，特别是可卡因、阿片类药物和酒精，如何改变伏隔核内侧壳中的 DA 释放，探讨了 DA/谷氨酸共同释放在介导这些效应中的潜在作用，并讨论了进一步研究这些机制的未来方向。
