Discriminative stimulus and reinforcing effects of p-fluoro-l-deprenyl in monkeys

Abstract

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