Acetylcholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine.
Release of the neurotransmitter dopamine in the mesolimbic system of the brain mediates the reinforcing properties of several drugs of abuse, including nicotine. Here we investigate the contribution of the high-affinity neuronal nicotinic acetylcholine receptor to the effects of nicotine on the mesolimbic dopamine system in mice lacking the beta2 subunit of this receptor. We found that nicotine stimulates dopamine release in the ventral striatum of wild-type mice but not in the ventral striatum of beta2-mutant mice. Using patch-clamp recording, we show that mesencephalic dopaminergic neurons from mice without the beta2 subunit no longer respond to nicotine, and that self-administration of nicotine is attenuated in these mutant mice. Our results strongly support the idea that the beta2-containing neuronal nicotinic acetylcholine receptor is involved in mediating the reinforcing properties of nicotine.
Picciotto
M R
MR
CNRS UA D1284, Neurobiologie Moléculaire, Institut Pasteur, Paris, France.
Zoli
M
M
Rimondini
R
R
Léna
C
C
Marubio
L M
LM
Pich
E M
EM
Fuxe
K
K
Changeux
J P
JP
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology; D003216:Conditioning, Operant; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D006719:Homovanillic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D017551:Microdialysis; D009043:Motor Activity; D009419:Nerve Tissue Proteins; D009538:Nicotine / Q000378:metabolism / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015290:Second Messenger Systems; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; D015102:3,4-Dihydroxyphenylacetic Acid; D009538:Nicotine; D003042:Cocaine; D000109:Acetylcholine; D004298:Dopamine; D006719:Homovanillic Acid