MAO inhibition increases sensitivity to nicotine’s rewarding properties in male and female rats.

Although tobacco use has one of the highest rates of addiction, animal models show nicotine to be weakly reinforcing. Tobacco smoke contains more than 4,000 compounds in addition to nicotine, including some that inhibit monoamine oxidase (MAO) activity in the brains of smokers. Recent studies have shown that inhibition of MAO dramatically increases the motivation to self‐administer nicotine in male rats. The present study compared the effect of MAO inhibition on the nicotine dose response curve in both male and female rats. Seven doses of nicotine (0, 1.25, 2.5, 5, 7.5, 10.5, 21, and 30 μg/kg/injection i.v.) were tested for acquisition of self‐administration behavior in rats pretreated 1 hour with tranylcypromine (3 mg/kg, i.p.), an irreversible non‐specific MAO inhibitor. It has previously been shown that the dose‐response curve for nicotine self‐administration is flat and truncated. However, with pretreatment of tranylcypromine, nicotine displayed a typical inverted‐U curve with an increased sensitivity to low doses of drug. Both sexes demonstrated a peak number of reinforced responses at a nicotine dose of 5 μg/kg, which, in the absence of tranylcypromine, is below the threshold for self‐administration. Whereas maximum nicotine intake occurred at this dose in females, males showed peak intake at a dose of 21 μg/kg nicotine. This study demonstrates that MAO inhibition greatly increases the sensitivity to the rewarding properties of nicotine in both males and females. The sex differences seen in drug intake will be investigated further by testing for potential motivational changes in drug seeking behavior. Supported by NIH grant DA 19138.