Reinforcement enhancing effect of nicotine and its attenuation by nicotinic antagonists in rats

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.