尼古丁对纹状体多巴胺释放的生理相关水平的调制。
Modulation of dopamine release in the striatum by physiologically relevant levels of nicotine.
机构信息
1] State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China [2].
State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
出版信息
Nat Commun. 2014 May 21;5:3925. doi: 10.1038/ncomms4925.
Striatal dopamine (DA) release can be independently triggered not only by action potentials (APs) in dopaminergic axons but also APs in cholinergic interneurons (ChIs). Nicotine causes addiction by modulating DA release, but with paradoxical findings. Here, we investigate how physiologically relevant levels of nicotine modulate striatal DA release. The optogenetic stimulation of ChIs elicits DA release, which is potently inhibited by nicotine with an IC50 of 28 nM in the dorsal striatum slice. This ChI-driven DA release is predominantly mediated by α6β2* nAChRs. Local electrical stimulus (Estim) activates both dopaminergic axons and ChIs. Nicotine does not affect the AP(DA)-dependent DA release (AP(DA), AP of dopaminergic axon). During burst Estim, nicotine permits the facilitation of DA release by prevention of DA depletion. Our work indicates that cholinergic stimulation-induced DA release is profoundly modulated by physiologically relevant levels of nicotine and resolves the paradoxical observation of nicotine's effects on striatal DA release.
纹状体多巴胺（DA）的释放不仅可以由多巴胺能轴突的动作电位（APs）独立触发，也可以由胆碱能中间神经元（ChIs）的 APs 触发。尼古丁通过调节 DA 释放引起成瘾，但存在矛盾的发现。在这里，我们研究了生理相关水平的尼古丁如何调节纹状体 DA 的释放。ChIs 的光遗传学刺激引发 DA 释放，尼古丁强烈抑制这种释放，在背侧纹状体切片中的 IC50 为 28 nM。这种 ChI 驱动的 DA 释放主要由α6β2*nAChRs 介导。局部电刺激（Estim）激活多巴胺能轴突和 ChIs。尼古丁不影响依赖于 AP 的 DA 释放（AP(DA)，多巴胺能轴突的 AP）。在爆发性 Estim 期间，尼古丁通过防止 DA 耗竭来促进 DA 释放。我们的工作表明，生理相关水平的尼古丁可以显著调节胆碱能刺激诱导的 DA 释放，并解决了尼古丁对纹状体 DA 释放影响的矛盾观察。
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