In rats trained to distinguish either the (+)- or (-)-isomer of MDMA from saline, both isomers of MDMA and MDA fully substituted for the training drugs. Stimulants like amphetamine and cocaine did not substitute. Hallucinogens such as DOM, LSD, and mescaline did not fully substitute for (+)-MDMA; LSD substituted for (-)-MDMA only at a specific dose. The serotonin-releasing agents fenfluramine and p-chloroamphetamine substituted partially or fully for both isomers. Serotonin receptor antagonists pirenpirone and metergoline did not consistently block MDMA's effects. The findings suggest that serotonin release, but not action at 5-HT(2) receptors, is important for the discriminative stimulus effects of MDMA isomers.
In rats trained to distinguish either the left- or right-handed form (isomer) of the drug MDA from saline, both isomers served as reliable cues at specific doses. The two isomers substituted for each other, and both were fully substituted by the related drug MDMA. The hallucinogens LSD and DOM substituted only for the left-handed isomer, while stimulants like amphetamine and cocaine did not produce MDA-like effects. The left-handed isomer's cue was blocked by a serotonin receptor antagonist, but dopamine blockers had no effect. Neither MDA isomer fully substituted for LSD or amphetamine cues, suggesting the left-handed isomer has more hallucinogen-like and serotonin-mediated effects, while both lack strong amphetamine-like properties.