title: Nicotinic, glutamatergic and dopaminergic synaptic transmission and plasticity in the mesocorticolimbic system: focus on nicotine effects.
abstract: 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.
authors.affiliation: CNR, Neuroscience Institute-Milano, Biometra University of Milan, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pistillo
authors.affiliation: CNR, Neuroscience Institute-Milano, Biometra University of Milan, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Clementi
authors.affiliation: Department of Biomedical, Metabolic and Neural Sciences, Section of Physiology and Neurosciences, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: michele.zoli@unimore.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Zoli
authors.affiliation: CNR, Neuroscience Institute-Milano, Biometra University of Milan, Milan, Italy. Electronic address: c.gotti@in.cnr.It.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gotti
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008032:Limbic System / Q000187:drug effects*; D009538:Nicotine / Q000378:metabolism / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D018698:Glutamic Acid; D009538:Nicotine; D004298:Dopamine
keywords: Mesocorticolimbic system; Nicotine; Nicotine addiction; Nucleus accumbens; Prefrontal cortex; Ventral tegmental area