Time course analysis of the discriminative stimulus effects of the optical isomers of 3,4-methylenedioxymethamphetamine (MDMA).

The present study examined the discriminative stimulus effects of the MDMA optical isomers administered at different presession injection intervals. In the first experiment, male Sprague-Dawley rats were trained in a two-lever, food-reinforced operant procedure to discriminate either (+)-MDMA (1.25 mg/kg) or (-)-MDMA (3.50 mg kg) at either 20 or 90 min following injection. Animals administered (+)-MDMA or saline 90 min before training sessions failed to attain the discrimination criteria after 73 training sessions, whereas (-)-MDMA successfully established discriminative stimulus control at both the 20 min and the 90 min postinjection intervals. (+)-Amphetamine did not substitute for either isomer, although a significant amount of drug-appropriate responding occurred in animals trained to discriminate (+)-MDMA at 20 min and (-)-MDMA at 90 min. Sch 39166 partially reduced the discrimination of (+)-MDMA at 20 min and (-)-MDMA at 90 min, although this effect was not dose dependent. Sch 39166 had no effect on animals trained to discriminate (-)-MDMA at 20 min. Haloperidol did not alter the discrimination of (+)-MDMA at 20 min but partially reduced the discriminative stimulus control of (-)-MDMA at 20 min and (-)-MDMA at 90 min. Fenfluramine substituted for both isomers of MDMA. Pirenpirone completely blocked the discriminative stimulus effects of (-)-MDMA at 20 min, although (+)-MDMA at 20 min and (-)-MDMA at 90 min were only partly blocked. WAY 100,135 had little effect on drug-appropriate responding; however, the discrimination of (+)-MDMA at 20 min was partly reduced by this 5-HT1A antagonist. In a second experiment, rats trained to discriminate (+)-MDMA (1.5 mg/kg) or (-)-MDMA (3.0 mg/kg) from saline were administered substitution tests with both isomers 20, 60, 90 and 120 min after injection. Results confirmed those of the first experiment that (+)-MDMA appears to have a shorter duration of action than (-)-MDMA. These results are discussed in light of the training doses employed.