Long-term effects of chronic nicotine exposure on brain nicotinic receptors.
Chronic nicotine exposure results in long-term homeostatic regulation of nicotinic acetylcholine receptors (nAChRs) that play a key role in the adaptative cellular processes leading to addiction. However, the relative contribution of the different nAChR subunits in this process is unclear. Using genetically modified mice and pharmacological manipulations, we provide behavioral, electrophysiological, and pharmacological evidence for a long-term mechanism by which chronic nicotine triggers opposing processes differentially mediated by beta2*- vs. alpha7*nAChRs. These data offer previously undescribed insights into the understanding of nicotine addiction and the treatment of several human pathologies by nicotine-like agents chronically acting on beta2*- or alpha7*nAChRs.
Besson
Morgane
M
Récepteurs et Cognition, Centre National de la Recherche Scientifique Unité de Recherche Associée 2182, Unité de Neurobiologie Intégrative des Systémes Cholinergiques, Institut Pasteur, 75724 Paris, France.
Granon
Sylvie
S
Mameli-Engvall
Monica
M
Cloëz-Tayarani
Isabelle
I
Maubourguet
Nicolas
N
Cormier
Anne
A
Cazala
Pierre
P
David
Vincent
V
Changeux
Jean-Pierre
JP
Faure
Philippe
P
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000633:toxicity*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000502:physiology; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000157:Aconitine; D009538:Nicotine; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; C054634:methyllycaconitine