http://www.cnr.it/ontology/cnr/individuo/prodotto/ID284749

Nicotine consumption is regulated by a human polymorphism in dopamine neurons (Articolo in rivista)

Type

Prodotto della ricerca (Classe)
Articolo in rivista (Classe)

Label

Nicotine consumption is regulated by a human polymorphism in dopamine neurons (Articolo in rivista) (literal)

Anno

2014-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

10.1038/mp.2013.158 (literal)

Alternative label

Morel C*; Fattore L*; Pons S; Hay YA; Marti F; Lambolez B; De Biasi M; Lathrop M; Fratta W; Maskos U; Faure P. *equal contribution. (2014)
Nicotine consumption is regulated by a human polymorphism in dopamine neurons
in Molecular psychiatry (Online)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Morel C*; Fattore L*; Pons S; Hay YA; Marti F; Lambolez B; De Biasi M; Lathrop M; Fratta W; Maskos U; Faure P. *equal contribution. (literal)

Pagina inizio

930 (literal)

Pagina fine

936 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url

http://www.scopus.com/inward/record.url?eid=2-s2.0-84904989473&partnerID=q2rCbXpz (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

19 (literal)

Rivista

Molecular psychiatry (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

8 (literal)

Note

Scopu (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

Neurobiologie des Processus Adaptatifs, CNRS UMR 7102, Equipe Neurophysiologie et Comportement (NPC), Boite 14, Université P. et M. Curie, 9 quai St Bernard, Paris, 75005, France; CNR Neuroscience Institute, Cagliari, National Research Council, Italy, Cittadella Universitaria, Monserrato, Italy; Institut Pasteur, Unité Neurobiologie intégrative des systèmes cholinergiques, CNRS UMR 3571, Paris, France; Université P. et M. Curie, CNRS UMR 7102, Neurobiologie des Processus Adaptatifs, Equipe Réseau cortical et couplage neurovasculaire, Paris, France; Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States; McGill University and Genome Quebec Innovation Centre, Montréal, QC, Canada; Fondation Jean Dausset, CEPH, Paris, France; Department of Biomedical Sciences, University of Cagliari Cittadella Universitaria, Monserrato, Italy (literal)

Titolo

Nicotine consumption is regulated by a human polymorphism in dopamine neurons (literal)

Abstract

Smoking is the most important preventable cause of morbidity and mortality worldwide. Recent genome-wide association studies highlighted a human haplotype on chromosome 15 underlying the risk for tobacco dependence and lung cancer. Several polymorphisms in the CHRNA3-CHRNA5-CHRNB4 cluster coding for the nicotinic acetylcholine receptor (nAChR) alpha3, alpha5 and alpha4 subunits were implicated. In mouse models, we define a key role in the control of sensitivity to nicotine for the alpha5 subunit in dopaminergic (DAergic) neurons of the ventral tegmental area (VTA). We first investigated the reinforcing effects of nicotine in drug-naive alpha5 -/- mice using an acute intravenous nicotine self-administration task and ex vivo and in vivo electrophysiological recordings of nicotine-elicited DA cell activation. We designed lentiviral re-expression vectors to achieve targeted re-expression of wild-type or mutant alpha5 in the VTA, in general, or in DA neurons exclusively. Our results establish a crucial role for alpha5*-nAChRs in DAergic neurons. These receptors are key regulators that determine the minimum nicotine dose necessary for DA cell activation and thus nicotine reinforcement. Finally, we demonstrate that a single-nucleotide polymorphism, the non-synonymous alpha5 variant rs16969968, frequent in many human populations, exhibits a partial loss of function of the protein in vivo. This leads to increased nicotine consumption in the self-administration paradigm. We thus define a critical link between a human predisposition marker, its expression in DA neurons and nicotine intake. (literal)

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