title: Targeted in vivo expression of nicotinic acetylcholine receptors in mouse brain using lentiviral expression vectors.
abstract: Nicotinic acetylcholine receptors (nAChRs) in the brain exhibit diverse functional properties and ubiquitous distribution. Yet, except for providing a receptor for the exogenously applied nicotine of tobacco products, their role in the normal functioning of the brain has remained elusive. We have used a lentiviral expression vector to re-express the beta2 subunit specifically in the ventral tegmental area (VTA) of beta2-/- mice. The viral vector efficiently expresses beta2- subunit protein leading to new nAChR-binding sites. VTA neurons transduced by the lentiviral vector are responsive to intravenous nicotine when analyzed using in vivo electrophysiology. Nicotine-induced dopamine release from the nucleus accumbens (NuAcc) was also restored in re-expressing beta2-/- mice. Intra-VTA injection of nicotine was found to be reinforcing in both wild-type and beta2-subunit re-expressing beta2-/- mice, but not in beta2-/- mice. Furthermore, in the absence of applied nicotine, the spontaneous slow exploratory behavior of the mice was restored, whereas fast navigation did not change. This latter behavioral analysis suggests a role for beta2* nAChR, specifically expressed in the VTA, in mammalian cognitive function.
authors.affiliation: Unité Récepteurs et Cognition, Institut Pasteur, 75724 Paris Cedex 15, France. bmolles@pasteur.fr
authors.forename: B E
authors.initials: BE
authors.lastname: Molles
authors.forename: U
authors.initials: U
authors.lastname: Maskos
authors.forename: S
authors.initials: S
authors.lastname: Pons
authors.forename: M
authors.initials: M
authors.lastname: Besson
authors.forename: P
authors.initials: P
authors.lastname: Guiard
authors.forename: J-P
authors.initials: JP
authors.lastname: Guilloux
authors.forename: A
authors.initials: A
authors.lastname: Evrard
authors.forename: A
authors.initials: A
authors.lastname: Cormier
authors.forename: M
authors.initials: M
authors.lastname: Mameli-Engvall
authors.forename: I
authors.initials: I
authors.lastname: Cloëz-Tayarani
authors.forename: H
authors.initials: H
authors.lastname: Nakatani
authors.forename: N
authors.initials: N
authors.lastname: Dufour
authors.forename: A-P
authors.initials: AP
authors.lastname: Bemelmans
authors.forename: J
authors.initials: J
authors.lastname: Mallet
authors.forename: P
authors.initials: P
authors.lastname: Cazala
authors.forename: A M
authors.initials: AM
authors.lastname: Gardier
authors.forename: V
authors.initials: V
authors.lastname: David
authors.forename: P
authors.initials: P
authors.lastname: Faure
authors.forename: S
authors.initials: S
authors.lastname: Granon
authors.forename: J-P
authors.initials: JP
authors.lastname: Changeux
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000235:genetics; D001921:Brain / Q000502:physiology*; D003071:Cognition / Q000502:physiology; D005106:Exploratory Behavior; D005822:Genetic Vectors; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009538:Nicotine; D011978:Receptors, Nicotinic / Q000172:deficiency / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D009538:Nicotine; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins