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 sti- mulation 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 a6b2* nAChRs. Local electrical stimulus (Estim) activates both dopaminergic axons and ChIs. Nicotine does not affect the APDA-dependent DA release (APDA, AP of dopaminergic axon). During burst Estim, nicotine permits the facilitation of DA release by prevention of DA depletion.

Zhuan Zhou's lab 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.

Li Wang1,*, Shujiang Shang1,*, Xinjiang Kang1,* etc (2014) Modulation of dopamine release in the striatum by physiologically relevant levels of nicotine.  NATURE COMMUNICATIONS  DOI: 10.1038/ncomms4925