ASSESSMENT OF THE DISCRIMINATIVE STIMULUS EFFECTS OF THE OPTICAL ISOMERS OF ECSTASY (3,4-METHYLENEDIOXYMETHAMPHETAMINE, MDMA)

The discriminative stimulus effects of the stereoisomers of 3,4-methyl enedioxymethamphetamine (MDMA) were studied in rats trained to discrim inate 1.25 mg/kg of (+)-MDMA or 3.5 mg/kg of (-)-MDMA from saline, in a two lever, water-reinforced, drug discrimination situation. The isom ers of MDMA and 3,4-methylenedioxyamphetamine (MDA) substituted comple tely for both training drugs. The stimulants amphetamine and cocaine d id not substitute for either MDMA isomer. The hallucinogens (+/-)-2,5- dimethoxy-4-methylamphetamine (DOM), (+)-lysergic acid diethylamide (L SD), and mescaline failed to substitute completely for (+)-MDMA. Simil arly, DOM and mescaline did not substitute for (-)-MDMA; however, LSD did substitute for this isomer at a dose of 0.06 mg/kg but not at high er doses. Substitution tests with 5-HT-releasing agents revealed that fenfluramine substituted partially for (+)-MDMA and completely for (-) -MDMA while p-chloroamphetamine substituted completely for both isomer s of MDMA. When given in combination with (+)-or (-)-MDMA, neither the 5-HT2 antagonist pirenpirone nor the less selective 5-HT antagonist m etergoline consistently blocked drug-appropriate responding. These res ults indicate that the stereoisomers of MDMA and MDA have similar disc riminative stimulus properties. More importantly, the present findings suggest that 5-HT release may be important for the discriminative sti mulus effects of(+)-and (-)-MDMA. Actions at 5-HT2 receptors, however, do not appear to be critical.