Reduction of withdrawal signs after chronic nicotine exposure of alpha-calcitonin gene-related peptide knock-out mice.
Nicotine, the main substance responsible for the addictive behavior of smokers, binds to a variety of nicotinic acetylcholine receptors (nAChRs) diversely distributed in the brain, notably in areas involved in motivation and reward mechanisms. The alpha-calcitonin gene-related peptide (alphaCGRP) has been previously shown to modulate the functions of nAChRs and is released in brain areas implicated in motivation, such as the amygdala or the ventral tegmental area. Interestingly, alphaCGRP -/- mice display a decrease in morphine withdrawal symptoms. In this context, we investigate the tolerance and withdrawal symptoms in alphaCGRP -/- mice exposed to acute and chronic nicotine. We report that these animals develop a normal tolerance to the antinociceptive effects of nicotine, but display an attenuation of somatic withdrawal symptoms.
Salmon
Anne-Marie
AM
CNRS UA D 1284 Récepteurs et Cognition, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
Evrard
Alexis
A
Damaj
Imad
I
Changeux
Jean-Pierre
JP
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009538:Nicotine / Q000008:administration & dosage*; D013375:Substance Withdrawal Syndrome / Q000235:genetics / Q000378:metabolism*; D014029:Tobacco Use Disorder / Q000235:genetics / Q000378:metabolism*
D009538:Nicotine; D015740:Calcitonin Gene-Related Peptide