Acetylcholine receptors containing the β2 subunit are involved in the reinforcing properties of nicotine

Marina R. Picciotto, Michele Zoli, Roberto Rimondini, Clément Léna, Lisa M. Marubio, Emilio Merlo Pich, Kjell Fuxe and Jean-Pierre Changeux
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Marina R. Picciotto: CNRS UA D1284, Neurobiologie Moléculaire, Institut Pasteur
Michele Zoli: CNRS UA D1284, Neurobiologie Moléculaire, Institut Pasteur
Roberto Rimondini: Karolinska Institute
Clément Léna: CNRS UA D1284, Neurobiologie Moléculaire, Institut Pasteur
Lisa M. Marubio: CNRS UA D1284, Neurobiologie Moléculaire, Institut Pasteur
Emilio Merlo Pich: Geneva Biomedical Research Institute, Glaxo-Wellcome R&D
Kjell Fuxe: Karolinska Institute
Jean-Pierre Changeux: CNRS UA D1284, Neurobiologie Moléculaire, Institut Pasteur

Nature, 1998, vol. 391, issue 6663, 173-177

Abstract: Abstract Release of the neurotransmitter dopamine in the mesolimbic system of the brain mediates the reinforcing properties of several drugs of abuse, including nicotine1. Here we investigate the contribution of the high-affinity neuronal nicotinic acetylcholine receptor2 to the effects of nicotine on the mesolimbic dopamine system in mice lacking the β2 subunit of this receptor3. We found that nicotine stimulates dopamine release in the ventral striatum of wild-type mice but not in the ventral striatum of β2-mutant mice. Using patch-clamp recording, we show that mesencephalic dopaminergic neurons from mice without the β2 subunit no longer respond to nicotine, and that self-administration of nicotine is attenuated in these mutant mice. Our results strongly support the idea that the β2-containing neuronal nicotinic acetylcholine receptor is involved in mediating the reinforcing properties of nicotine.

Date: 1998
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DOI: 10.1038/34413

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