MDMA and its enantiomers increase affiliative social behaviors and vocalizations in group-housed squirrel monkeys, while methamphetamine has only modest effects. Pretreatment with a 5-HT_2A receptor antagonist or a 5-HT_2C receptor agonist reduces MDMA-induced social behaviors, whereas a 5-HT_1A receptor antagonist does not affect affiliative vocalizations and even increases social contact. These results indicate that the prosocial effects of MDMA depend on 5-HT_2A, but not 5-HT_1A, receptors, aligning with findings in humans and rodents. Understanding these neurochemical mechanisms may aid in developing therapeutics that retain MDMA's social benefits with fewer drawbacks.
MDMA has both stimulant and hallucinogen-like effects, and its two isomers, R(−)-MDMA and S(+)-MDMA, produce different behavioral effects: R(−)-MDMA is hallucinogen-like, while S(+)-MDMA is stimulant-like. In this study, mice were trained to discriminate each isomer from a vehicle in a two-lever operant task. Drugs with hallucinogen-like effects (2C-T-7, DPT) and stimulant-like effects (amphetamine, cocaine) were substituted for the training isomer. Results showed efficacy differences within chemical classes and potency differences within behavioral classes, clarifying the complex discriminative stimulus properties of MDMA isomers.