Discriminative stimulus and reinforcing effects of p-fluoro-L-deprenyl in monkeys.
BACKGROUND
para-Fluoro-L-deprenyl (Fludepryl), a halogenated derivative of L-deprenyl, shares structural similarities with amphetamine and may have potential as a medication for psychostimulant abuse.


OBJECTIVE
p-Fluoro-L-deprenyl was evaluated for psychomotor stimulant, discriminative stimulus, and reinforcing effects in squirrel monkeys.


METHODS
One group of monkeys was trained under a ten-response fixed-ratio (FR10) schedule of stimulus termination to discriminate between methamphetamine (0.32 mg/kg, i.m.) and saline. Other monkeys were trained to self-administer i.v. cocaine under either a simple FR10 schedule or a second-order fixed-interval 5-min schedule with FR10 components.


RESULTS
Full generalization to the methamphetamine-training stimulus was produced by an i.m. dose of 10.0 mg/kg p-fluoro-L-deprenyl. L-Deprenyl and the metabolites of p-fluoro-L-deprenyl, p-fluoro-L-amphetamine, and p-fluoro-L-methylamphetamine were more potent, producing full generalization at doses of 1.0-3.2 mg/kg. Under the FR10 schedule of drug injection, persistent self-administration behavior was maintained by i.v. cocaine injections but not by injections of vehicle or injection doses of p-fluoro-L-deprenyl up to 1.0 mg/kg. However, p-fluoro-L-deprenyl did maintain moderate levels of i.v. self-administration responding under the second-order schedule of drug injection. Peak response rates maintained by 0.1-mg/kg injections of p-fluoro-L-deprenyl were significantly greater than those associated with saline substitution, yet significantly lower than those maintained by cocaine or D-amphetamine.


CONCLUSIONS
p-Fluoro-L-deprenyl has methamphetamine-like discriminative-stimulus properties in squirrel monkeys that appear at higher doses than for its parent compound, L-deprenyl. It also appears to function as a relatively limited reinforcer of intravenous self-administration behavior in monkeys trained to self-administer i.v. cocaine.
Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Sevil
S
Yasar
Jozsef
J
Gaal
Zuzana
Z
Justinova
Jack
J
Bergman
D019969:Amphetamine-Related Disorders / Q000523:psychology; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001245:Association Learning / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005795:Generalization, Stimulus; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008694:Methamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology; D009042:Motivation; D012055:Reinforcement Schedule; D012453:Saimiri; D012642:Selegiline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012646:Self Administration; D013329:Structure-Activity Relationship
D000662:Amphetamines; D000697:Central Nervous System Stimulants; C508014:p-fluoro-L-amphetamine; C508013:p-fluoro-L-deprenyl; D012642:Selegiline; D008694:Methamphetamine; D003042:Cocaine; D003913:Dextroamphetamine