Journal
PSYCHOPHARMACOLOGY
Volume 184, Issue 3-4, Pages 339-344Publisher
SPRINGER
DOI: 10.1007/s00213-005-0295-x
Keywords
nicotine; reward; conditioned place preference; nicotinic acetylcholine receptor; alpha 7 subunit; beta 2 subunit; mice
Categories
Funding
- NIDA NIH HHS [DA-05274, DA-12610, DA-07027] Funding Source: Medline
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Rationale: 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. Objecitives: 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 alpha 4 beta 2 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 alpha 7 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 beta 2 subunit of the nAChR did not exhibit nicotine CPP while alpha 7 knock-out mice did. Conclusion: Taken together, these data suggest that the beta 2 subunit of the nAChR is critically involved in nicotine reward as measured by CPP.
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