Acetylcholine receptors containing the 2 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 & Jean-Pierre Changeux
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 2 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 2-mutant mice. Using patch-clamp recording, we show that mesencephalic dopaminergic neurons from mice without the 2 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 2-containing neuronal nicotinic acetylcholine receptor is involved in mediating the reinforcing properties of nicotine.