PT  - JOURNAL ARTICLE
AU  - Nicolas Champtiaux
AU  - Cecilia Gotti
AU  - Matilde Cordero-Erausquin
AU  - Denis J. David
AU  - Cédric Przybylski
AU  - Clément Léna
AU  - Francesco Clementi
AU  - Milena Moretti
AU  - Francesco M. Rossi
AU  - Nicolas Le Novère
AU  - J. Michael McIntosh
AU  - Alain M. Gardier
AU  - Jean-Pierre Changeux
TI  - Subunit Composition of Functional Nicotinic Receptors in Dopaminergic Neurons Investigated with Knock-Out Mice
AID  - 10.1523/JNEUROSCI.23-21-07820.2003
DP  - 2003 Aug 27
TA  - The Journal of Neuroscience
PG  - 7820--7829
VI  - 23
IP  - 21
4099  - http://www.jneurosci.org/content/23/21/7820.short
4100  - http://www.jneurosci.org/content/23/21/7820.full
SO  - J. Neurosci.2003 Aug 27; 23
AB  - Nicotinic acetylcholine receptors (nAChRs) expressed by dopaminergic (DA) neurons have long been considered as potential therapeutic targets for the treatment of several neuropsychiatric diseases, including nicotine and cocaine addiction or Parkinson's disease. However, DA neurons express mRNAs coding for most, if not all, neuronal nAChR subunits, and the subunit composition of functional nAChRs has been difficult to establish. Immunoprecipitation experiments performed on mouse striatal extracts allowed us to identify three main types of heteromeric nAChRs (α4β2*, α6β2*, and α4α6β2*) in DA terminal fields. The functional relevance of these subtypes was then examined by studying nicotine-induced DA release in striatal synaptosomes and recording ACh-elicited currents in DA neurons fromα4, α6, α4α6, and β2 knock-out mice. Our results establish that α6β2* nAChRs are functional and sensitive to α-conotoxin MII inhibition. These receptors are mainly located on DA terminals and consistently do not contribute to DA release induced by systemic nicotine administration, as evidenced by in vivo microdialysis. In contrast, (nonα6)α4β2* nAChRs represent the majority of functional heteromeric nAChRs on DA neuronal soma. Thus, whereas a combination of α6β2* and α4β2* nAChRs may mediate the endogenous cholinergic modulation of DA release at the terminal level, somato-dendritic (nonα6)α4β2* nAChRs most likely contribute to nicotine reinforcement.