Discriminative stimulus effects of hallucinogens and psychostimulants in S(+)‐MDMA, and R(−)‐MDMA trained mice

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.

Study at a glance

Abstract

3,4‐Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative with increasingly widespread abuse. MDMA has been difficult to classify as a stimulant or hallucinogen because it shares effects with both drug classes. Furthermore, racemic MDMA is composed of two isomers that vary in terms of behavioral effects rather than simple potency differences. Specifically, the R(−) isomer of MDMA has hallucinogen like effects whereas the S(+) isomer has stimulant like effects. In the present study, mice were trained under a liquid food reinforcer two lever operant paradigm to discriminate S(+) or R(−)‐MDMA from vehicle. Drugs that are hallucinogen like and either structurally similar (2,5‐dimethoxy‐4‐(n)‐propylthiophenethylamine ‐ 2C‐T‐7) or not (N,N‐Dipropyltryptamine ‐ DPT) and drugs that are stimulant like and either structurally similar (Amphetamine) or not (Cocaine) were substituted for the training drug in mice trained to discriminate each isomer. Within chemical class we have found apparent efficacy differences whereas within behavioral class we have found potency differences. These studies enlighten our understanding of the complex nature of the discriminative stimulus properties of MDMA.