| Literature DB >> 21502501 |
Richard Exley1, Nicolas Maubourguet, Vincent David, Raphaël Eddine, Alexis Evrard, Stéphanie Pons, Fabio Marti, Sarah Threlfell, Pierre Cazala, J Michael McIntosh, Jean-Pierre Changeux, Uwe Maskos, Stephanie J Cragg, Philippe Faure.
Abstract
Nicotine is the primary psychoactive component of tobacco. Its reinforcing and addictive properties depend on nicotinic acetylcholine receptors (nAChRs) located within the mesolimbic axis originating in the ventral tegmental area (VTA). The roles and oligomeric assembly of subunit α4- and subunit α6-containing nAChRs in dopaminergic (DAergic) neurons are much debated. Using subunit-specific knockout mice and targeted lentiviral re-expression, we have determined the subunit dependence of intracranial nicotine self-administration (ICSA) into the VTA and the effects of nicotine on dopamine (DA) neuron excitability in the VTA and on DA transmission in the nucleus accumbens (NAc). We show that the α4 subunit, but not the α6 subunit, is necessary for ICSA and nicotine-induced bursting of VTA DAergic neurons, whereas subunits α4 and α6 together regulate the activity dependence of DA transmission in the NAc. These data suggest that α4-dominated enhancement of burst firing in DA neurons, relayed by DA transmission in NAc that is gated by nAChRs containing α4 and α6 subunits, underlies nicotine self-administration and its long-term maintenance.Entities:
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Year: 2011 PMID： 21502501 PMCID： PMC3088627 DOI： 10.1073/pnas.1103000108
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205