TY - JOUR AU - Xiao Cheng AU - Zhou Chun-yi AU - Jiang Jin-hong AU - Yin Cui PY - 2020 TI - Neural circuits and nicotinic acetylcholine receptors mediate the cholinergic regulation of midbrain dopaminergic neurons and nicotine dependence JF - Acta Pharmacologica Sinica; Vol 41, No 1 (January 2020): Acta Pharmacologica Sinica Y2 - 2020 KW - N2 - Midbrain dopaminergic (DA) neurons are governed by an endogenous cholinergic system, originated in the mesopontine nuclei. Nicotine hijacks nicotinic acetylcholine receptors (nAChRs) and interferes with physiological function of the cholinergic system. In this review, we describe the anatomical organization of the cholinergic system and the key nAChR subtypes mediating cholinergic regulation of DA transmission and nicotine reward and dependence, in an effort to identify potential targets for smoking intervention. Cholinergic modulation of midbrain DA systems relies on topographic organization of mesopontine cholinergic projections, and activation of nAChRs in midbrain DA neurons. Previous studies have revealed that α4, α6, and β2 subunit-containing nAChRs expressed in midbrain DA neurons and their terminals in the striatum regulate ﬁrings of midbrain DA neurons and activity-dependent dopamine release in the striatum. These nAChRs undergo modiﬁcation upon chronic nicotine exposure. Clinical investigation has demonstrated that partial agonists of these receptors elevate the success rate of smoking cessation relative to placebo. However, further investigations are required to reﬁne the drug targets to mitigate unpleasant side-effects. UR - http://www.chinaphar.com/article/view/10068