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.(ABSTRACT TRUNCATED AT 250 WORDS)
Yasar
S
S
Behavioral Pharmacology and Genetics Section, National Institute on Drug Abuse Addiction Research Center, Baltimore, Maryland.
Schindler
C W
CW
Thorndike
E B
EB
Szelenyi
I
I
Goldberg
S R
SR
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D004193:Discrimination Learning; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004435:Eating; D004558:Electric Stimulation; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012642:Selegiline / Q000494:pharmacology*; D013237:Stereoisomerism
D000662:Amphetamines; D012642:Selegiline