title: Alpha7-nicotinic receptors modulate nicotine-induced reinforcement and extracellular dopamine outflow in the mesolimbic system in mice.
abstract: BACKGROUND
  Nicotine is the main addictive component of tobacco and modifies brain function via its action on neuronal acetylcholine nicotinic receptors (nAChRs). The mesolimbic dopamine (DA) system, where neurons of the ventral tegmental area (VTA) project to the nucleus accumbens (ACb), is considered a core site for the processing of nicotine's reinforcing properties. However, the precise subtypes of nAChRs that mediate the rewarding properties of nicotine and that contribute to the development of addiction remain to be identified.
  
  
  OBJECTIVE
  We investigated the role of the nAChRs containing the α7 nicotinic subunit (α7 nAChRs) in the reinforcing properties of nicotine within the VTA and in the nicotine-induced changes in ACb DA outflow in vivo.
  
  
  METHODS
  We performed intra-VTA self-administration and microdialysis experiments in genetically modified mice lacking the α7 nicotinic subunit or after pharmacological blockade of α7 nAChRs in wild-type mice.
  
  
  RESULTS
  We show that the reinforcing properties of nicotine within the VTA are lower in the absence or after pharmacological blockade of α7 nAChRs. We also report that nicotine-induced increases in ACb DA extracellular levels last longer in the absence of these receptors, suggesting that α7 nAChRs regulate the action of nicotine on DA levels over time.
  
  
  CONCLUSIONS
  The present results reveal new insights for the role of α7 nAChRs in modulating the action of nicotine within the mesolimbic circuit. These receptors appear to potentiate the reinforcing action of nicotine administered into the VTA while regulating its action over time on DA outflow in the ACb.
authors: Unité Neurobiologie Intégrative des Systèmes Cholinergiques, Unité de Recherche Associée 2182, Centre National de la recherche Scientifique, Institut Pasteur, 75015 Paris, France. morgane.besson@pasteur.fr
authors: Morgane
authors: M
authors: Besson
authors: Vincent
authors: V
authors: David
authors: Mathieu
authors: M
authors: Baudonnat
authors: Pierre
authors: P
authors: Cazala
authors: Jean-Philippe
authors: JP
authors: Guilloux
authors: Christelle
authors: C
authors: Reperant
authors: Isabelle
authors: I
authors: Cloez-Tayarani
authors: Jean-Pierre
authors: JP
authors: Changeux
authors: Alain M
authors: AM
authors: Gardier
authors: Sylvie
authors: S
authors: Granon
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D017551:Microdialysis; D009474:Neurons / Q000378:metabolism; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D012054:Reinforcement, Psychology; D012201:Reward; D012646:Self Administration; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579166:Chrna7 protein, mouse; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; D004298:Dopamine