Distinct contributions of nicotinic acetylcholine receptor subunit α4 and subunit α6 to the reinforcing effects of nicotine

被引：114

作者：

Exley, Richard ^{[2
]}

Maubourguet, Nicolas ^{[1
]}

David, Vincent ^{[3
]}

Eddine, Raphael ^{[4
]}

Evrard, Alexis ^{[1
]}

Pons, Stephanie ^{[1
]}

Marti, Fabio ^{[4
]}

Threlfell, Sarah ^{[2
]}

Cazala, Pierre ^{[3
]}

McIntosh, J. Michael ^{[5
,6
]}

Changeux, Jean-Pierre ^{[1
]}

Maskos, Uwe ^{[1
]}

Cragg, Stephanie J. ^{[2
]}

Faure, Philippe ^{[1
,4
]}

机构：

[1] Inst Pasteur, CNRS, URA 2182, Unite Neurobiol Integrat Syst Cholinerg, F-75724 Paris 15, France

[2] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3PT, England

[3] Univ Bordeaux 2, Ctr Neurosci Integrat & Cognit, CNRS, UMR 5228, Talence, France

[4] Univ Paris 06, CNRS, UMR 7102, F-75005 Paris, France

[5] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA

[6] Univ Utah, Dept Psychiat, Salt Lake City, UT 84112 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 18期

基金：

英国医学研究理事会;

关键词：

electrophysiology; lentivirus; nicotinic receptor; voltammetry; ventral striatum; VENTRAL TEGMENTAL AREA; MIDBRAIN DOPAMINE NEURONS; BRAIN REWARD AREAS; FIRING PATTERN; MICE LACKING; NUCLEUS-ACCUMBENS; RELEASE; MODULATION; STRIATUM; SYSTEM;

D O I：

10.1073/pnas.1103000108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页码：7577 / 7582

页数：6

共 44 条

[1]

α-Conotoxin MII-Sensitive Nicotinic Acetylcholine Receptors in the Nucleus Accumbens Shell Regulate Progressive Ratio Responding Maintained by Nicotine [J].