A comparison of drug-seeking behavior maintained by D-amphetamine, L-deprenyl (selegiline), and D-deprenyl under a second-order schedule in squirrel monkeys.
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.
Yasar
Sevil
S
Preclinical Pharmacology Section, Behavioral Neurosciences Research Branch, DHHS/NIH/NIDA Intramural Research Program, Baltimore, MD 21224, USA. syasar@jhmi.edu
Gaál
József
J
Panlilio
Leigh V
LV
Justinova
Zuzana
Z
Molnár
Szecsö V
SV
Redhi
Godfrey H
GH
Schindler
Charles W
CW
D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D012055:Reinforcement Schedule; D012453:Saimiri; D012642:Selegiline / Q000737:chemistry / Q000494:pharmacology*; D012646:Self Administration; D013237:Stereoisomerism; D019966:Substance-Related Disorders / Q000523:psychology*
D000697:Central Nervous System Stimulants; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D008995:Monoamine Oxidase; D003913:Dextroamphetamine