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A mechanism of modulating dopamine release in the striatum by smoking-level nicotine

Li Wang  Ruiying Jiao  Wei Liu  Huadong Xu  Feipeng Zhu  Xiaoxuan Sun  Li Zhou  Minli Li  Qinglong Wang  Sasa Teng  Changhe Wang  周专  
【摘要】:Striatal dopamine(DA)release can be independently triggered by two pathways,the midbrain nigrostriatal ascending pathway and the cholinergic transmission-induced dopaminergic transmission(CTDT)pathway.Smoking–level nicotine(SL-nicotine)causes addiction by modulating DA release,but with paradoxical observations.Here,we investigated how SL-nicotine modulates DA release following optogenetics-induced CTDT in striatal slices.We found that(1)SL-nicotine abolished DA release via CTDT but not the ascending pathway;(2)an electrical-field stimulus(Estim)triggered DA release with 2phases of DA(2p DA),corresponding to ascending and CDTD pathways;(3)following a single Estim,SL-nicotine reduced the depletion of DA vesicle pool;(4)during a burst Estim,SL-nicotine inhibited the initial component but facilitated the 2*n ACh Rs wereβ6alater component of 2p DA due to reduced DA depletion;(5)responsible for striatal CTDT.Our work resolves the paradoxical observations of 2*n ACh Rs and CTDT as targets to treatβ6aEstim-induced DA release and offer smoking addiction.

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