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 metabolized in part to l-methamphetamine and l-amphetamine. As the clinical use of amphetamine-like psychostimulants is limited by their potential for abuse, we evaluated l-deprenyl for amphetamine-like discriminative stimulus effects over a range of experimental conditions. Male Fisher rats were trained under a 5-response, fixed-ratio schedule of stimulus-shock termination or a 10- response, fixed-ratio schedule of food-presentation to discriminate between d-amphetamine (1.0 mg/kg i.p.) and saline in a two-lever, operant conditioning procedure. Full generalization was obtained to l-amphetamine (1.0-2.0 mg/kg), d-deprenyl (10.0-17.0 mg/kg) and l-deprenyl (17.0 and 30.0 mg/kg) under both the food-presentation and stimulus-shock termination schedules, and increases in responding on the lever appropriate to d- amphetamine were dose-dependent. The dose-effect functions for l-amphetamine, l-deprenyl and d-deprenyl were shifted slightly to the left under the stimulus-shock termination schedule compared to the food-presentation schedule. When l-deprenyl (3.0 or 5.6 mg/kg i.p.) was given 30 min before d- amphetamine it produced a small shift to the left in the dose-effect function for d-amphetamine under the food-presentation schedule. l-Deprenyl produced clear generalization to the d-amphetamine stimulus only at very high doses of 17.0 to 30.0 mg/kg, doses about 10-fold higher than those that have a selective action on MAO-B vs. MAO-A and which start to have marked rate decreasing actions on food-reinforced responding. Thus, the present findings are in accord with clinical findings that over almost 20 years of long-term clinical use l-deprenyl has shown no signs of abuse liability.