A 3-LEVER OPERANT PROCEDURE DIFFERENTIATES THE STIMULUS EFFECTS OF R(-)-MDA FROM S(-MDA())

1-(3,4-Methylenedioxyphenyl)-2-aminopropane (MDA) produces an effect i n humans that is somewhat similar to both a hallucinogen and a central stimulant. We have previously shown that R(-)-MDA but not S(+)-MDA pr oduces a stimulus effect in animals similar to that of the hallucinoge n 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), whereas S(+)) -MDA but not R(-)-MDA produces a stimulus effect similar to that of th e stimulant amphetamine. Others have suggested that the stimulus effec ts of the two MDA isomers may be much more similar than our results wo uld indicate. To help clarify this issue, we have shown that rats (n = 8) can be trained to discriminate 1.25 mg/kg of R(-)-MDA (ED(50) = 0. 99 mg/kg) from 1.25 mg/kg of S(+)-MDA (ED(50) = 0.80 mg/kg) versus 0.9 % saline with use of a three-lever operant procedure. To accomplish th is task it was necessary to institute a separation of 4 days between i njections of the isomers. In tests of stimulus substitution, the admin istration of various doses of DOM (ED(50) = 0.47 mg/kg), S(+)-DOM (ED( 50) = 2.23 mg/kg) and mescaline (ED(50) = 16.04 mg/kg) produced dose-r elated responding on the R(-)-MDA-appropriate lever. In contrast, the injection of various doses of S(+)-amphetamine (ED(50) = 0.46 mg/kg) a nd cocaine (ED(50) = 6.40 mg/kg) produced dose-related responding on t he S(+)-MDA-appropriate lever. The administration of racemic MDA, at t wice the isomer training dose, resulted in the animals dividing their responses closely between the R(-)-MDA- and S(+)-MDA-designated levers . In antagonism tests, the serotonin-2 antagonist pirenperone blocked the stimulus effect of 1.25 mg/kg of R(-)-MDA but had no effect on the stimulus effect of 1.25 mg/kg of S(+)-MDA. Taken together, these data support the contention that each optical isomer of MDA can produce a markedly different stimulus effect.