Dopamine is involved in physiological processes like learning and memory, motor control and reward, and pathological conditions such as Parkinson's disease and addiction. In contrast to the extensive studies on neurons, astrocyte involvement in dopaminergic signaling remains largely unknown. Using transgenic mice, optogenetics, and pharmacogenetics, we studied the role of astrocytes on the dopaminergic system. We show that in freely behaving mice, astrocytes in the nucleus accumbens (NAc), a key reward center in the brain, respond with Ca2+ elevations to synaptically released dopamine, a phenomenon enhanced by amphetamine. In brain slices, synaptically released dopamine increases astrocyte Ca2+, stimulates ATP/adenosine release, and depresses excitatory synaptic transmission through activation of presynaptic A1 receptors. Amphetamine depresses neurotransmission through stimulation of astrocytes and the consequent A1 receptor activation. Furthermore, astrocytes modulate the acute behavioral psychomotor effects of amphetamine. Therefore, astrocytes mediate the dopamine- and amphetamine-induced synaptic regulation, revealing a novel cellular pathway in the brain reward system.

中文翻译：

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伏隔核中多巴胺诱发的突触调节需要星形胶质细胞活动。

多巴胺参与学习和记忆、运动控制和奖励等生理过程，以及帕金森病和成瘾等病理状况。与对神经元的广泛研究相反，星形胶质细胞参与多巴胺能信号传导在很大程度上仍然未知。使用转基因小鼠、光遗传学和药物遗传学，我们研究了星形胶质细胞在多巴胺能系统中的作用。我们表明，在行为自由的小鼠中，伏隔核 (NAc) 中的星形胶质细胞是大脑中的一个关键奖赏中心，它会以 Ca2+ 升高对突触释放的多巴胺做出反应，这种现象会因安非他明而增强。在脑切片中，突触释放的多巴胺增加星形胶质细胞 Ca2+，刺激 ATP/腺苷释放，并通过激活突触前 A1 受体抑制兴奋性突触传递。苯丙胺通过刺激星形胶质细胞和随后的 A1 受体激活来抑制神经传递。此外，星形胶质细胞调节苯丙胺的急性行为精神运动效应。因此，星形胶质细胞介导多巴胺和苯丙胺诱导的突触调节，揭示了大脑奖赏系统中的一种新细胞通路。