The monoamine oxidase inhibitor phenelzine enhances the discriminative stimulus effect of nicotine in rats

Abstract

In addition to delivering nicotine, tobacco smoke also inhibits monoamine oxidase (MAO). Although MAO inhibitors (MAOIs) can increase nicotine self-administration in rodents, the effects of MAOIs on the discriminative stimulus effect of nicotine are not known. This study examined the effects of three MAOIs (phenelzine, clorgyline and pargyline) with varying selectivity for MAO_A and MAO_B in the nicotine drug discrimination procedure in rats. Adult male Sprague–Dawley rats were trained to discriminate nicotine (0.3 mg/kg, subcutaneously) from saline in a standard, two-lever food-reinforced operant task. Once the discrimination was acquired, the ability of each MAOI to substitute for or alter the discriminative stimulus effect of nicotine was determined. In substitution tests, nicotine (0.03–0.3 mg/kg) produced full, dose-dependent substitution. Although the selective MAO_A inhibitor clorgyline (3–56 mg/kg) and the selective MAO_B inhibitor pargyline (3–56 mg/kg) did not elicit any nicotine-appropriate responding, partial substitution was obtained with the nonselective MAO inhibitor phenelzine (1–17 mg/kg). Phenelzine (10 mg/kg) also enhanced the discriminative stimulus effect of a low dose of nicotine (0.056 mg/kg) and prolonged the time course effect of the nicotine-training dose. These findings indicate that concomitant inhibition of MAO_A and MAO_B can enhance the discriminative stimulus effect of nicotine in rats.