期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 18, 页码 7577-7582出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1103000108
关键词
electrophysiology; lentivirus; nicotinic receptor; voltammetry; ventral striatum
资金
- Institut Pasteur, Centre National de la Recherche Scientifique Unite de Recherche Associee [2182]
- Unite Mixte de Recherche [7102, 5228]
- Agence Nationale de Recherches programme Neuroscience, Neurology and Psychiatry
- Agence Nationale de Recherches
- Medical Research Council (United Kingdom) [G0700932]
- Parkinson's Disease Society (United Kingdom) [G0808]
- European Union [HEALTH-F2-2008-202088]
- Network of European Neuroscience Institutes (ENI-NET)
- Pierre Fabre Laboratories
- Fondation Gilbert Lagrue
- Bettencourt Foundation
- MRC [G0700932] Funding Source: UKRI
- Medical Research Council [G0700932] Funding Source: researchfish
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 alpha 4- and subunit alpha 6-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 alpha 4 subunit, but not the alpha 6 subunit, is necessary for ICSA and nicotine-induced bursting of VTA DAergic neurons, whereas subunits alpha 4 and alpha 6 together regulate the activity dependence of DA transmission in the NAc. These data suggest that alpha 4-dominated enhancement of burst firing in DA neurons, relayed by DA transmission in NAc that is gated by nAChRs containing alpha 4 and alpha 6 subunits, underlies nicotine self-administration and its long-term maintenance.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据