, Volume 183, Issue 4, pp 413-421

A comparison of drug-seeking behavior maintained by d-amphetamine, l-deprenyl (selegiline), and d-deprenyl under a second-order schedule in squirrel monkeys

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Abstract

l-Deprenyl (selegiline) is used in the treatment of Parkinson’s disease and has been proposed as an aid for cigarette smoking cessation and a treatment for psychostimulant abuse. l-Deprenyl is metabolized in the body to l-methamphetamine and l-amphetamine, suggesting that it may have abuse potential. The current study assessed whether l-deprenyl or its isomer would maintain drug-seeking behavior on a second-order schedule and whether l-deprenyl would alter drug-seeking behavior maintained by d-amphetamine if given as a pretreatment. Squirrel monkeys learned to respond on a second-order schedule of reinforcement, where every tenth response was followed by a brief light flash, and the first brief light flash after 30 min was paired with intravenous (i.v.) injection of d-amphetamine (0.56 mg/kg), administered over a 2-min period at the end of the session. When responding was stable, saline or different i.v. doses of d-amphetamine (0.3–1.0 mg/kg), l-deprenyl (0.1–10.0 mg/kg), and d-deprenyl (0.1–3.0 mg/kg) were substituted for 10 days each. Subsequently, monkeys were pretreated with 0.3 or 1.0 mg/kg l-deprenyl intramuscularly 30 min prior to d-amphetamine baseline sessions. d-Amphetamine maintained high rates of drug-seeking behavior on the second-order schedule. d-Deprenyl maintained high rates of drug-seeking behavior similar to d-amphetamine. l-Deprenyl maintained lower rates of responding that were not significantly above saline substitution levels. Pretreatment with l-deprenyl failed to alter drug-seeking behavior maintained by d-amphetamine. These results indicate that d-deprenyl, but not l-deprenyl, may have abuse potential. Under conditions where drug-seeking and drug-taking behaviors are actively maintained by d-amphetamine, l-deprenyl, at doses that specifically inhibit type B monoamine oxidase, may not be effective as a treatment.