EVALUATION OF THE STEREOISOMERS OF DEPRENYL FOR AMPHETAMINE-LIKE DISCRIMINATIVE STIMULUS EFFECTS IN RATS

The antiparkinsonian agent l-deprenyl, a selective monoamine oxidase ( MAO)-B inhibitor, is a phenylalkylamine derivative which is metabolize d in part to /-methamphetamine and l-amphetamine. As the clinical use of amphetamine-like psychostimulants is limited by their potential for abuse, we evaluated 1-deprenyl for amphetamine-like discriminative st imulus effects over a range of experimental conditions. Male Fisher ra ts were trained under a 5-response, fixed-ratio schedule of stimulus-s hock termination or a 1 0-response, fixed-ratio schedule of food-prese ntation to discriminate between d-amphetamine (1.0 mg/kg i.p.) and sal ine in a two-lever, operant conditioning procedure. Full generalizatio n was obtained to l-amphetamine (1.0-2.0 mg/kg), d-deprenyl (10.0-17.0 mg/kg) and /-deprenyl (17.0 and 30.0 mg/kg) under both the food-prese ntation and stimulus-shock termination schedules, and increases in res ponding on the lever appropriate to d-amphetamine were dose-dependent. The dose-effect functions for l-amphetamine, l-deprenyl and d-depreny l were shifted slightly to the left under the stimulus-shock terminati on schedule compared to the food-presentation schedule. When l-depreny l (3.0 or 5.6 mg/kg i.p.) was given 30 min before d-amphetamine it pro duced a small shift to the left in the dose-effect function for d-amph etamine under the food-presentation schedule. l-Deprenyl produced clea r generalization to the d-amphetamine stimulus only at very high doses of 17.0 to 30.0 mg/kg, doses about 1 0-fold higher than those that ha ve a selective action on MAO-B vs. MAO-A and which start to have marke d rate decreasing actions on food-reinforced responding. Thus, the pre sent findings are in accord with clinical findings that over almost 20 years of long-term clinical use l-deprenyl has shown no signs of abus e liability.