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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Distinct contributions of nicotinic acetylcholine receptor subunit oc4 and subunit oc6 to the reinforcing effects of nicotine
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Distinct contributions of nicotinic acetylcholine receptor subunit oc4 and subunit oc6 to the reinforcing effects of nicotine

机译：烟碱乙酰胆碱受体亚基oc4和亚基oc6对尼古丁增强作用的不同贡献

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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 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 a4 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 a4 and ot6 subunits, underlies nicotine self-administration and its long-term maintenance.
机译：尼古丁是烟草的主要精神活性成分。它的增强和成瘾性取决于烟酸乙酰胆碱受体（nAChRs）位于源自腹侧被盖区（VTA）的中边缘边缘。多巴胺能（DAergic）神经元中α4亚基和α6亚基nAChRs的作用和寡聚装配备受争议。使用亚基特异性基因敲除小鼠和靶向的慢病毒再表达，我们已经确定了颅内尼古丁自我施用（ICSA）进入VTA的亚基依赖性以及尼古丁对VTA中多巴胺（DA）神经元兴奋性和DA传递的影响在伏伏核（NAc）中。我们显示，α4亚基而不是α6亚基对于ICSA和尼古丁诱导的VTA DA能神经元爆发是必需的，而亚基a4和α6一起调节NAc中DA传递的活性依赖性。这些数据表明，α4为主的DA神经元爆发放电的增强，是由NAc中DA传递所传递，而DA传递是由包含a4和ot6亚基的nAChRs控制的，是尼古丁自我给药及其长期维持的基础。

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  • 作者

    Richard Exley; Nicolas Maubourguet; Vincent David; Raphaël Eddine; Alexis Evrard; Stephanie Pons; Fabio Marti; Sarah Threlfell; Pierre Cazala; J. Michael Mclntosh; Jean-Pierre Changeux; Uwe Maskos; Stephanie J. Cragg; Philippe Faure;

  • 作者单位

    Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford 0X1 3PT, United Kingdom;

    Centre National de la Recherche Scientifique,Unite de Recherche Associee 2182, Unite Neurobiologie Integrative des Systemes Cholinergiques, Institut Pasteur, 75724 Paris Cedex 15, France;

    Centre National de la Recherche Scientifique, Unite Mixte de Recherche 5228, Centre de Neurosciences Integratives et Cognitives, Universite Bordeaux 2, Talence,France;

    Universite Pierre et Marie Curie, Centre National de la Recherche Scientifique, Unite Mixte de Recherche 7102, 75005 Paris, France;

    Centre National de la Recherche Scientifique,Unite de Recherche Associee 2182, Unite Neurobiologie Integrative des Systemes Cholinergiques, Institut Pasteur, 75724 Paris Cedex 15, France;

    Centre National de la Recherche Scientifique,Unite de Recherche Associee 2182, Unite Neurobiologie Integrative des Systemes Cholinergiques, Institut Pasteur, 75724 Paris Cedex 15, France;

    Universite Pierre et Marie Curie, Centre National de la Recherche Scientifique, Unite Mixte de Recherche 7102, 75005 Paris, France;

    Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford 0X1 3PT, United Kingdom;

    Centre National de la Recherche Scientifique, Unite Mixte de Recherche 5228, Centre de Neurosciences Integratives et Cognitives, Universite Bordeaux 2, Talence,France;

    Biology, University of Utah, Salt Lake City, UT 84112,Psychiatry, University of Utah, Salt Lake City, UT 84112;

    Centre National de la Recherche Scientifique,Unite de Recherche Associee 2182, Unite Neurobiologie Integrative des Systemes Cholinergiques, Institut Pasteur, 75724 Paris Cedex 15, France;

    Centre National de la Recherche Scientifique,Unite de Recherche Associee 2182, Unite Neurobiologie Integrative des Systemes Cholinergiques, Institut Pasteur, 75724 Paris Cedex 15, France;

    Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford 0X1 3PT, United Kingdom;

    Centre National de la Recherche Scientifique,Unite de Recherche Associee 2182, Unite Neurobiologie Integrative des Systemes Cholinergiques, Institut Pasteur, 75724 Paris Cedex 15, France,Universite Pierre et Marie Curie, Centre National de la Recherche Scientifique, Unite Mixte de Recherche 7102, 75005 Paris, France;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    electrophysiology; lentivirus; nicotinic receptor; voltammetry; ventralstriatum;

    机译：电生理;慢病毒;烟碱受体;伏安法;腹侧纹状体;

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