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- Title
Nicotinic Acetylcholine Receptors in the Mesolimbic Pathway: Primary Role of Ventral Tegmental Area α6β2* Receptors in Mediating Systemic Nicotine Effects on Dopamine Release, Locomotion, and Reinforcement.
- Authors
Gotti, Cecilia; Guiducci, Stefania; Tedesco, Vincenzo; Corbioli, Silvia; Zanetti, Lara; Moretti, Milena; Zanardi, Alessio; Rimondini, Roberto; Mugnaini, Manolo; Clementi, Francesco; Chiamulera, Christian; Zoli, Michele
- Abstract
α6* nicotinic acetylcholine receptors (nAChRs) are highly and selectively expressed by mesostriatal dopamine (DA) neurons. These neurons are thought to mediate several behavioral effects of nicotine, including locomotion, habit learning, and reinforcement. Yet the functional role ofα6* nAChRs in midbrain DA neurons is mostly unknown. The aim of this study was to determine the composition and in vivo functional role ofα6* nAChR in mesolimbic DA neurons of male rats. Immunoprecipitation and immunopurification techniques coupled with cell-specific lesions showed that the composition of α6* nAChR in the mesostriatal system is heterogeneous, with (non- α4)α6β2* being predominant in the mesolimbic pathway and α4α6β2* in the nigrostriatal pathway. We verified whetherα6* receptors mediate the systemic effects of nicotine on the mesolimbicDApathway by perfusing the selective antagonists α-conotoxin MII (CntxMII) (α3/α6β2* selective) or α-conotoxin PIA (CntxPIA) (α6β2* selective) into ventral tegmental area (VTA). The intra-VTA perfusion of CntxMII or CntxPIA markedly decreased systemic nicotine-elicited DA release in the nucleus accumbens and habituated locomotion; the intra-VTA perfusion of CntxMII also decreased the rate of nicotine infusion in the maintenance phase of nicotine, but not of food, self-administration. Overall, the results of these experiments show that the α6β2* nAChRs expressed in the VTA are necessary for the effects of systemic nicotine on DA neuron activity and DA-dependent behaviors such as locomotion and reinforcement, and suggest that α6α2*-selective compounds capable of crossing the blood- brain barrier may affect the addictive properties of nicotine and therefore be useful in the treatment of tobacco dependence.
- Subjects
CHOLINERGIC receptors; NICOTINIC receptors; DOPAMINE; NEURONS; LOCOMOTION; TOBACCO
- Publication
Journal of Neuroscience, 2010, Vol 30, Issue 15, p5311
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.5095-09.2010