Nicotine enhances alcohol intake and dopaminergic responses through β2* and β4* nicotinic acetylcholine receptors.

Abstract : Alcohol and nicotine are the most widely co-abused drugs. Both modify the activity of dopaminergic (DA) neurons of the Ventral Tegmental Area (VTA) and lead to an increase in DA release in the Nucleus Accumbens, thereby affecting the reward system. Evidences support the hypothesis that distinct nicotinic acetylcholine receptors (nAChRs), the molecular target of acetylcholine (ACh) and exogenous nicotine, are also in addition implicated in the response to alcohol. The precise molecular and neuronal substrates of this interaction are however not well understood. Here we used in vivo electrophysiology in the VTA to characterise acute and chronic interactions between nicotine and alcohol. Simultaneous injections of the two drugs enhanced their responses on VTA DA neuron firing and chronic exposure to nicotine increased alcohol-induced DA responses and alcohol intake. Then, we assessed the role of β4 * nAChRs, but not β2 * nAChRs, in mediating acute responses to alcohol using nAChR subtypes knockout mice (β2-/- and β4-/- mice). Finally, we showed that nicotine-induced modifications of alcohol responses were absent in β2-/- and β4-/- mice, suggesting that nicotine triggers β2* and β4 * nAChR-dependent neuroadaptations that subsequently modify the responses to alcohol and thus indicating these receptors as key mediators in the complex interactions between these two drugs.
Type de document :
Article dans une revue
Scientific Reports, Nature Publishing Group, 2017, 7, pp.45116. <10.1038/srep45116>
Liste complète des métadonnées


http://hal.upmc.fr/hal-01502363
Contributeur : Gestionnaire Hal-Upmc <>
Soumis le : mercredi 5 avril 2017 - 14:03:31
Dernière modification le : lundi 19 juin 2017 - 10:24:49

Fichier

srep45116.pdf
Publication financée par une institution

Licence


Distributed under a Creative Commons Paternité 4.0 International License

Identifiants

Collections

Citation

Stefania Tolu, Fabio Marti, Carole Morel, Carole Perrier, Nicolas Torquet, et al.. Nicotine enhances alcohol intake and dopaminergic responses through β2* and β4* nicotinic acetylcholine receptors.. Scientific Reports, Nature Publishing Group, 2017, 7, pp.45116. <10.1038/srep45116>. <hal-01502363>

Partager

Métriques

Consultations de
la notice

57

Téléchargements du document

16