Genetic dissociation of two behaviors associated with nicotine addiction: beta-2 containing nicotinic receptors are involved in nicotine reinforcement but not in withdrawal syndrome.
BACKGROUND
Nicotine addiction is characterized by two distinct behaviors, chronic compulsive self-administration and the induction of a withdrawal syndrome upon cessation of nicotine consumption.


OBJECTIVE
To examine if these two processes rely on beta2-containing nicotinic receptors--beta2*nAChRs--we analyzed the behavior of mice lacking these receptors in the two situations.


RESULTS
First, we showed that, in contrast to wild-type (WT) mice, beta2-knockout (beta2-/-) mice exhibit no intra-ventral tegmental area (VTA) nicotine self-administration, whereas their ability to self-administer morphine is intact. However, beta2-/- mice showed some sensitivity to locomotor effects of nicotine, implying an effect of the drug on other nicotinic subtypes. Then, we observed that beta2-/- mice exhibited a normal nicotine withdrawal syndrome, i.e., increased levels of rearing and jumping upon precipitated withdrawal. Thus, the beta2*nAChRs are not involved in the behaviors induced by cessation of nicotine consumption.


CONCLUSIONS
Taken together, the present data demonstrated a genetic dissociation of two distinct behavioral patterns associated with nicotine addiction. They further suggested that independent molecular mechanisms underlie these two aspects, offering the possibility of controlling them separately.
Besson
M
M
Unité CNRS 2182 Récepteurs & Cognition, Département de Neuroscience, Institut Pasteur, 25 rue du Dr. Roux, 75015 Paris, France.
David
V
V
Suarez
S
S
Cormier
A
A
Cazala
P
P
Changeux
J-P
JP
Granon
S
S
D000818:Animals; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000008:administration & dosage; D009538:Nicotine / Q000008:administration & dosage / Q000633:toxicity*; D011978:Receptors, Nicotinic / Q000235:genetics*; D012054:Reinforcement, Psychology; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics*; D017557:Ventral Tegmental Area / Q000187:drug effects
D009020:Morphine; D009538:Nicotine; D011978:Receptors, Nicotinic