An oral self-administration model of nicotine preference in rats: effects of mecamylamine.

A new oral model of nicotine self-administration in rats has been described. The model utilizes a two-lever operant procedure with rats having a choice between nicotine and water reinforcement. Most (16 of 20) rats exhibited reliable preferences for nicotine solutions equal to or less than 32 micrograms/ml; preferences were inversely related to the concentration of nicotine. Mecamylamine (0.25-5.0 mg/kg), a nicotinic antagonist, reduced preferences for a low nicotine concentration (4 micrograms/ml) and enhanced preferences for a high nicotine concentration (32 micrograms/ml). The relationship of nicotine concentration to nicotine preference appeared to be consistent with previous reports of nicotine self-administration using the intravenous route in rats as well as the respiratory route (i.e., smoking) in humans. The mecamylamine-induced changes in nicotine preference were consistent with its nicotinic antagonist action as well as with effects of mecamylamine reported in humans. This model should be useful in the preclinical assessment of new agents as potential therapies in smoking cessation programs.