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Discriminative stimulus effects of psychostimulants and hallucinogens in S(+)-MDMA and R(-)-MDMA tra

Discriminative stimulus effects of psychostimulants and hallucinogens in S(+)-MDMA and R(-)-MDMA tra

  1. Jatelka
    Journal of Pharmacology and Experimental Therapeutics 2009 Aug 14. [Epub ahead of print]

    Murnane KS, Murai N, Howell LL, Fantegrossi WE.

    3,4-Methylenedioxymethamphetamine (MDMA) is a substituted phenethylamine more commonly known as the drug of abuse "ecstasy." The acute and persistent neurochemical effects of MDMA in the mice are distinct from those in other species. MDMA shares biological effects with both amphetamine-type stimulants and mescaline-type hallucinogens, which may be attributable to distinct effects of its two enantiomers, both of which are active in vivo. In this regard, among the substituted phenethylamines, R(-)- enantiomers tend to have hallucinogen-like effects whereas S(+)- enantiomers tend to have stimulant-like effects. In the present study, mice were trained to discriminate S(+)- or R(-)-MDMA from vehicle. Drug substitution tests were then undertaken with the structurally similar phenethylamine dopamine / norepinephrine releaser S(+)-amphetamine, the structurally dissimilar tropane nonselective monoamine reuptake inhibitor cocaine, the structurally similar phenethylamine 5-HT2A agonist 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7), and the structurally dissimilar mixed action tryptamine 5-HT2A agonist / monoamine reuptake inhibitor N,N dipropyltryptamine (DPT). S(+)-amphetamine fully substituted in the S(+)-MDMA treated animals but did not substitute for the R(-)-MDMA cue. 2C-T-7 fully substituted in the R(-)-MDMA trained animals but did not substitute for the S(+)-MDMA cue. Cocaine and DPT substituted for both training drugs, but while cocaine was more potent in S(+)-MDMA-trained mice, DPT was more potent in R(-)-MDMA-trained mice. These data suggest that qualitative differences in the discriminative stimulus effects of each stereoisomer of MDMA exist in mice, and further our understanding of the complex nature of the interoceptive effects of MDMA.