Modulation of dopamine release in the striatum by physiologically relevant levels of nicotine

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 relevan...

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Bibliographic Details
Published in:Nature communications 2014-05, Vol.5 (1), p.3925-3925, Article 3925
Main Authors: Wang, Li, Shang, Shujiang, Kang, Xinjiang, Teng, Sasa, Zhu, Feipeng, Liu, Bin, Wu, Qihui, Li, Mingli, Liu, Wei, Xu, Huadong, Zhou, Li, Jiao, Ruiying, Dou, Haiqiang, Zuo, Panli, Zhang, Xiaoyu, Zheng, Lianghong, Wang, Shirong, Wang, Changhe, Zhou, Zhuan
Format: Article
Language:English
Subjects:
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Animals
Corpus Striatum - metabolism
Corpus Striatum - physiology
Dopamine - metabolism
Electric Stimulation
Humanities and Social Sciences
In Vitro Techniques
Mice
Mice, Transgenic
multidisciplinary
Nicotine - metabolism
Science
Science (multidisciplinary)
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Summary: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 IC 50 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. Nicotine exposure from cigarette smoke modulates dopamine release in the brain, which is implicated in nicotine addiction, but how it does this is unclear. Here, in mouse brain slices, the authors show that nicotine inhibits cholinergic- but not dopaminergic-dependent dopamine release.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms4925