Targeted in vivo expression of nicotinic acetylcholine receptors in mouse brain using lentiviral expression vectors.
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.
Molles
B E
BE
Unité Récepteurs et Cognition, Institut Pasteur, 75724 Paris Cedex 15, France. bmolles@pasteur.fr
Maskos
U
U
Pons
S
S
Besson
M
M
Guiard
P
P
Guilloux
J-P
JP
Evrard
A
A
Cormier
A
A
Mameli-Engvall
M
M
Cloëz-Tayarani
I
I
Nakatani
H
H
Dufour
N
N
Bemelmans
A-P
AP
Mallet
J
J
Cazala
P
P
Gardier
A M
AM
David
V
V
Faure
P
P
Granon
S
S
Changeux
J-P
JP
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
D009538:Nicotine; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins