期刊
MOLECULAR PSYCHIATRY
卷 18, 期 3, 页码 382-393出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2012.83
关键词
dopamine; GABAergic interneuron; lentiviral vector; nicotine addiction; nicotinic acetylcholine receptor
资金
- Institut Pasteur
- Centre National de la Recherche Scientifique CNRS [URA 2182, UMR 7102, UMR 5287]
- ATIP programme
- Agence Nationale pour la Recherche (ANR Neuroscience, Neurologie et Psychiatrie) [ANR BLANC 2009]
- Neuropole IdF
- INSERM [U960]
- RTRA Ecole des Neurosciences de Paris
- Bettencourt Schueller Foundation
- European Union [HEALTH-F2-2008-202088]
- Fondation de la Recherche Medicale (FRM)
- Pasteur-Weizmann
Smoking is the most important preventable cause of mortality and morbidity worldwide. This nicotine addiction is mediated through the nicotinic acetylcholine receptor (nAChR), expressed on most neurons, and also many other organs in the body. Even within the ventral tegmental area (VTA), the key brain area responsible for the reinforcing properties of all drugs of abuse, nicotine acts on several different cell types and afferents. Identifying the precise action of nicotine on this microcircuit, in vivo, is important to understand reinforcement, and finally to develop efficient smoking cessation treatments. We used a novel lentiviral system to re-express exclusively high-affinity nAChRs on either dopaminergic (DAergic) or gamma-aminobutyric acid-releasing (GABAergic) neurons, or both, in the VTA. Using in vivo electrophysiology, we show that, contrary to widely accepted models, the activation of GABA neurons in the VTA plays a crucial role in the control of nicotine-elicited DAergic activity. Our results demonstrate that both positive and negative motivational values are transmitted through the dopamine (DA) neuron, but that the concerted activity of DA and GABA systems is necessary for the reinforcing actions of nicotine through burst firing of DA neurons. This work identifies the GABAergic interneuron as a potential target for smoking cessation drug development. Molecular Psychiatry (2013) 18, 382-393; doi:10.1038/mp.2012.83; published online 3 July 2012
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