Pistillo Francesco, Clementi Francesco, Zoli Michele, Gotti Cecilia
CNR, Neuroscience Institute-Milano, Biometra University of Milan, Milan, Italy.
Department of Biomedical, Metabolic and Neural Sciences, Section of Physiology and Neurosciences, University of Modena and Reggio Emilia, Modena, Italy.
Prog Neurobiol. 2015 Jan;124:1-27. doi: 10.1016/j.pneurobio.2014.10.002. Epub 2014 Nov 3.
Cigarette smoking is currently the leading cause of preventable deaths and disability throughout the world, being responsible for about five million premature deaths/year. Unfortunately, fewer than 10% of tobacco users who try to stop smoking actually manage to do so. The main addictive agent delivered by cigarette smoke is nicotine, which induces psychostimulation and reward, and reduces stress and anxiety. The use of new technologies (including optogenetics) and the development of mouse models characterised by cell-specific deletions of receptor subtype genes or the expression of gain-of-function nAChR subunits has greatly increased our understanding of the molecular mechanisms and neural substrates of nicotine addiction first revealed by classic electrophysiological, neurochemical and behavioural approaches. It is now becoming clear that various aspects of nicotine dependence are mediated by close interactions of the glutamatergic, dopaminergic and γ-aminobutyric acidergic systems in the mesocorticolimbic system. This review is divided into two parts. The first provides an updated overview of the circuitry of the ventral tegmental area, ventral striatum and prefrontal cortex, the neurotransmitter receptor subtypes expressed in these areas, and their physiological role in the mesocorticolimbic system. The second will focus on the molecular, functional and behavioural mechanisms involved in the acute and chronic effects of nicotine on the mesocorticolimbic system.
目前，吸烟是全球可预防死亡和残疾的首要原因，每年导致约500万人过早死亡。不幸的是，试图戒烟的烟草使用者中，实际成功戒烟的不到10%。香烟烟雾中的主要成瘾物质是尼古丁，它能引起精神兴奋和奖赏感，并减轻压力和焦虑。新技术（包括光遗传学）的应用以及通过细胞特异性缺失受体亚型基因或表达功能增强型烟碱型乙酰胆碱受体亚基构建的小鼠模型，极大地增进了我们对尼古丁成瘾分子机制和神经基础的理解，这些机制最初是通过经典的电生理、神经化学和行为学方法揭示的。现在越来越清楚的是，尼古丁依赖的各个方面是由中脑边缘系统中谷氨酸能、多巴胺能和γ-氨基丁酸能系统的密切相互作用介导的。本综述分为两部分。第一部分提供腹侧被盖区、腹侧纹状体和前额叶皮质神经回路的最新概述，这些区域表达的神经递质受体亚型，以及它们在中脑边缘系统中的生理作用。第二部分将聚焦于尼古丁对中脑边缘系统急性和慢性影响所涉及的分子、功能和行为机制。
