Monoamine oxidase A rather than monoamine oxidase B inhibition increases nicotine reinforcement in rats

Abstract

Although nicotine is considered to be responsible for the addictive properties of tobacco, growing evidence underlines the importance of non‐nicotine components in smoking reinforcement. It has been shown that tobacco smoke contains monoamine oxidase (MAO) A and B inhibitors and decreases MAO‐A and MAO‐B activity in smokers. Here, we investigated the effects of clorgyline hydrochloride (irreversible MAO‐A inhibitor; 2 mg/kg/day), selegiline (irreversible MAO‐B inhibitor; 4 mg/kg) and the beta‐carboline norharmane hydrochloride (reversible MAO‐B inhibitor; 5 mg/kg/day) treatments on nicotine self‐administration (30 µg/kg/infusion, free base) in rats. Independent of the responsiveness to novelty and locomotor activity stimulation, only clorgyline hydrochloride treatment increased the intake of nicotine in a fixed‐ratio schedule (FR5) of reinforcement. When a progressive‐ratio schedule was implemented, both clorgyline hydrochloride and norharmane hydrochloride treatments potentiated the reinforcing effects of nicotine, whereas selegiline had no effect. Taken together, these results indicate that MAO‐A inhibition interacts with nicotine to enhance its rewarding effects in rats and suggest that other compounds present in tobacco, such as beta‐carboline, may also play an important role in sustaining smoking behavior in humans.