The beta2 but not alpha7 subunit of the nicotinic acetylcholine receptor is required for nicotine-conditioned place preference in mice.
BACKGROUND
Tobacco use is implicated in approximately 440,000 deaths per year, making it the leading cause of preventable death in the United States. Although it is generally recognized that tobacco use is correlated with a variety of health-related complications, many smokers are unsuccessful in their efforts to stop smoking using current cessation therapies.


OBJECTIVE
Given that nicotine is the addictive component of tobacco, successful smoking cessation therapies must address the various processes, including reward, which contribute to nicotine addiction. As such, determining the nicotinic receptor subtypes involved in nicotine reward is of utmost importance to understanding how nicotine addiction progresses.


METHODS
Conditioned place preference (CPP) in three-chamber conditioning boxes was performed. For antagonist studies, drug was given on all conditioning sessions 10 min before nicotine or saline injection and placement in the boxes.


RESULTS
We have demonstrated that a pretreatment with the alpha4beta2 subunit of the nicotinic acetylcholine receptor (nAChR) antagonist dihydro-beta-erythroidine (2.0 mg/kg, s.c.) blocked nicotine (0.5 mg/kg, s.c.) CPP in wild-type mice (C57BL/6 mice). In contrast, pretreatment with an antagonist of the alpha7 subunit of the nAChR, methyllycaconitine (MLA, 5.0 or 10.0 mg/kg, s.c.), had no effect on this behavior. Finally, we showed that mice lacking the beta2 subunit of the nAChR did not exhibit nicotine CPP while alpha7 knock-out mice did.


CONCLUSIONS
Taken together, these data suggest that the beta2 subunit of the nAChR is critically involved in nicotine reward as measured by CPP.
Walters
Carrie L
CL
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA. cwalters@vcu.edu
Brown
Sharon
S
Changeux
Jean-Pierre
JP
Martin
Billy
B
Damaj
M Imad
MI
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002755:Choice Behavior / Q000502:physiology*; D003213:Conditioning, Psychological / Q000502:physiology*; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D005260:Female; D006579:Heterozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009042:Motivation; D011292:Premedication; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D012055:Reinforcement Schedule; D012931:Social Environment; D014029:Tobacco Use Disorder / Q000235:genetics / Q000503:physiopathology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000157:Aconitine; D004079:Dihydro-beta-Erythroidine; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579166:Chrna7 protein, mouse; C054634:methyllycaconitine