A comparison of drug-seeking behavior maintained by D: -amphetamine, L: -deprenyl (selegiline), and D: -deprenyl under a second-order schedule in squirrel monkeys
by
Yasar S, Gaal J, Panlilio LV, Justinova Z,
Molnar SV, Redhi GH, Schindler CW.
Preclinical Pharmacology Section,
Behavioral Neurosciences Research Branch,
DHHS/NIH/NIDA Intramural Research Program,
Baltimore, MD, 21224, USA.
Psychopharmacology (Berl). 2005 Nov 15;:1-9

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.

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