期刊
PSYCHOPHARMACOLOGY
卷 194, 期 4, 页码 463-473出版社
SPRINGER
DOI: 10.1007/s00213-007-0863-3
关键词
nicotine; nonpharmacological stimuli; reinforcement-enhancing effect; nicotinic acetylcholine receptors; mecamylamine; dihydro-beta-erythroidine; methyllycaconitine
资金
- NIDA NIH HHS [DA17288, R01 DA017288, R01 DA010464, R01 DA010464-11, DA10464, R01 DA037277, R01 DA017288-04] Funding Source: Medline
Rationale Recent studies have demonstrated that nicotine can enhance operant responding for other nonpharmacological reinforcing stimuli. However, the nature of the reinforcement-enhancing effect of nicotine remains largely unknown. Objective The present study determined the dose dependency of the ability of nicotine to increase lever-pressing responses maintained by a compound visual stimulus (VS) in rats and examined its sensitivity to pharmacological antagonism of nicotinic acetylcholine receptors (nAChRs). Materials and methods Male Sprague-Dawley rats were trained in daily 1-h sessions to lever press for delivery of a VS (1 s lever light on and 60 s house light off) on a fixed ratio 5 schedule. During these sessions, eight scheduled response-independent intravenous infusions of nicotine (total amount: 0, 0.06, 0.12, 0.24, 0.48 mg kg(-1) h(-1)) were delivered. In pharmacological tests, a nonselective nAChR antagonist mecamylamine, alpha 4 beta 2-selective antagonist dihydro-beta-erythroidine (DH beta E), and alpha 7-selective antagonist methyllycaconitine (MLA) were administered in different groups of rats 30 min before the session. Results The VS maintained a moderate level of lever-pressing responses and nicotine dose-dependently increased responses for the VS presentations. Preteatment of mecamylamine and DH beta E but not MLA significantly attenuated the nicotine-enhanced responding. However, mecamylamine had no effect on responding for the VS in rats that received scheduled saline infusions. Conclusions These results demonstrate dose dependency of the reinforcement-enhancing effect of nicotine and suggest that activation of the alpha 4 beta 2- but not alpha 7-containing nAChRs may mediate this effect.
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