Time course analysis of the discriminative stimulus effects of the optical isomers of...

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.