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Alpha7-nicotinic receptors modulate nicotine-induced reinforcement and extracellular dopamine outflow in the mesolimbic system in mice

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Abstract

Rationale

Nicotine is the main addictive component of tobacco and modifies brain function via its action on neuronal acetylcholine nicotinic receptors (nAChRs). The mesolimbic dopamine (DA) system, where neurons of the ventral tegmental area (VTA) project to the nucleus accumbens (ACb), is considered a core site for the processing of nicotine’s reinforcing properties. However, the precise subtypes of nAChRs that mediate the rewarding properties of nicotine and that contribute to the development of addiction remain to be identified.

Objectives

We investigated the role of the nAChRs containing the α7 nicotinic subunit (α7*nAChRs) in the reinforcing properties of nicotine within the VTA and in the nicotine-induced changes in ACb DA outflow in vivo.

Methods

We performed intra-VTA self-administration and microdialysis experiments in genetically modified mice lacking the α7 nicotinic subunit or after pharmacological blockade of α7*nAChRs in wild-type mice.

Results

We show that the reinforcing properties of nicotine within the VTA are lower in the absence or after pharmacological blockade of α7*nAChRs. We also report that nicotine-induced increases in ACb DA extracellular levels last longer in the absence of these receptors, suggesting that α7*nAChRs regulate the action of nicotine on DA levels over time.

Conclusions

The present results reveal new insights for the role of α7*nAChRs in modulating the action of nicotine within the mesolimbic circuit. These receptors appear to potentiate the reinforcing action of nicotine administered into the VTA while regulating its action over time on DA outflow in the ACb.

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Acknowledgements

This work was supported by Institut Pasteur and Centre National de la Recherche Scientifique. MB was supported by Fondation pour la Recherche Médicale. The authors would like to thank Uwe Maskos, Philippe Faure and David Belin for valuable discussion. The authors would like to thank Ruth McNamara for the correction of English.

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Author notes

  1. Isabelle Cloez-Tayarani

    Present address: Unité de Génétique Humaine et Fonctions Cognitives, Institut Pasteur, 75015, Paris, France

  2. Sylvie Granon

    Present address: Centre de Neurosciences Paris Sud XI, CNRS UMR 8195, Université Paris-Sud, 91405, Orsay Cedex, France

Authors and Affiliations

  1. Unité Neurobiologie Intégrative des Systèmes Cholinergiques, Unité de Recherche Associée 2182, Centre National de la recherche Scientifique, Institut Pasteur, 75015, Paris, France

    Morgane Besson, Isabelle Cloez-Tayarani, Jean-Pierre Changeux & Sylvie Granon

  2. Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, CNRS UMR 5287, Université de Bordeaux, 33405, Talence, France

    Vincent David, Mathieu Baudonnat & Pierre Cazala

  3. EA 3544, Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry Cedex, 92296, France

    Jean-Philippe Guilloux, Christelle Reperant & Alain M. Gardier

  4. Unité Neurobiologie Intégrative des Systèmes Cholinergiques, Institut Pasteur, 25 rue du Dr. Roux, 75015, Paris, France

    Morgane Besson

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  1. Morgane Besson
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Correspondence to Morgane Besson.

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M. Besson and V. David equally contributed to the work.

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Besson, M., David, V., Baudonnat, M. et al. Alpha7-nicotinic receptors modulate nicotine-induced reinforcement and extracellular dopamine outflow in the mesolimbic system in mice. Psychopharmacology 220, 1–14 (2012). https://doi.org/10.1007/s00213-011-2422-1

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