ASSESSMENT OF THE MDA AND MDMA OPTICAL ISOMERS IN A STIMULANT-HALLUCINOGEN DISCRIMINATION

The phenylisopropylamine derivatives 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) have been compared to both psychostimulants and hallucinogens in drug discrimination investi gations. The stereoisomers of these compounds, in particular those of MDA, appear to produce differential effects. Previous studies have dem onstrated that animals trained to discriminate amphetamine from vehicl e generalize to the S(+)-isomers but not the R(-)-isomers of MDA and M DMA while animals trained to discriminate LSD from saline generalize t o R(-)-MDA and neither isomer of MDMA. However, animals trained to dis criminate mescaline from vehicle generalize to both stereoisomers of t hese phenylisopropylamine derivatives. The present study consisted of two experiments in which a three-choice drug discrimination procedure was employed to compare the stereoisomers of MDA and MDMA to both amph etamine and either mescaline (experiment one) or LSD (experiment two). Sixteen male Sprague-Dawley rats were trained to discriminate S(+)-am phetamine (1.0 mg/kg) and mescaline (12.5 mg/kg) and eight rats were t rained to discriminate S(+)-amphetamine (1.0 mg/kg) and LSD (0.08 mg/k g) from saline in three-choice, food reinforced drug discrimination pr ocedures. Substitution tests were administered with the isomers of MDA and MDMA. In the second experiment, substitution tests were also admi nistered with lower doses of each training compound and with the stimu lant cocaine and the hallucinogen 2,5-dimethoxy-4-methylphenylisopropy lamine (DOM). In both experiments, all of the isomers produced very fe w responses on the S(+)-amphetamine lever. In the first experiment, R( -)-MDA and R(-)-MDMA produced nearly complete substitution for mescali ne. The results of the second experiment revealed partial substitution for LSD with both isomers of MDMA and S(+)-MDA, and nearly complete s ubstitution with R(-)MDA for LSD. The present findings do not support previous reports that S(+)-MDMA and S(+)-MDA substitute for S(+)-amphe tamine. The three-lever drug discrimination procedure may provide a mo re sensitive behavioral assay in which to examine the discriminative s timulus effects of drugs with compound stimulus properties. (C) 1997 E lsevier Science Inc.