Assessment of the MDA and MDMA optical isomers in a stimulant-hallucinogen discrimination.
L E Baker, M M Taylor
Pharmacology, Biochemistry, and Behavior August 1997 DOI: 10.1016/s0091-3057(96)00334-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study using a three-choice drug discrimination procedure Peer reviewed |
|---|---|
| Sample size | 24 |
| Population | Male Sprague-Dawley rats |
| Interventions | MDMA MDA S(+)-amphetamine mescaline LSD cocaine DOM |
| Dose | S(+)-amphetamine 1.0 mg/kg, mescaline 12.5 mg/kg, LSD 0.08 mg/kg |
| Topics | MDMA |
| Key findings | All isomers of MDA and MDMA produced few responses on the amphetamine lever. R(-)-MDA and R(-)-MDMA substituted nearly completely for mescaline, and R(-)-MDA substituted nearly completely for LSD, while both MDMA isomers and S(+)-MDA partially substituted for LSD. These results do not support previous reports that S(+)-MDMA substitutes for amphetamine. |
Abstract
The phenylisopropylamine derivatives 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) have been compared to both psychostimulants and hallucinogens in drug discrimination investigations. The stereoisomers of these compounds, in particular those of MDA, appear to produce differential effects. Previous studies have demonstrated that animals trained to discriminate amphetamine from vehicle generalize to the S(+)-isomers but not the R(-)-isomers of MDA and MDMA while animals trained to discriminate LSD from saline generalize to R(-)-MDA and neither isomer of MDMA. However, animals trained to discriminate mescaline from vehicle generalize to both stereoisomers of these 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 amphetamine and either mescaline (experiment one) or LSD (experiment two). Sixteen male Sprague-Dawley rats were trained to discriminate S(+)-amphetamine (1.0 mg/kg) and mescaline (12.5 mg/kg) and eight rats were trained to discriminate S(+)-amphetamine (1.0 mg/kg) and LSD (0.08 mg/kg) from saline in three-choice, food reinforced drug discrimination procedures. Substitution tests were administered with the isomers of MDA and MDMA. In the second experiment, substitution tests were also administered with lower doses of each training compound and with the stimulant cocaine and the hallucinogen 2,5-dimethoxy-4-methylphenylisopropylamine (DOM). In both experiments, all of the isomers produced very few responses on the S(+)-amphetamine lever. In the first experiment, R(-)-MDA and R(-)-MDMA produced nearly complete substitution for mescaline. The results of the second experiment revealed partial substitution for LSD with both isomers of MDMA and S(+)-MDA, and nearly complete substitution with R(-)MDA for LSD. The present findings do not support previous reports that S(+)-MDMA and S(+)-MDMA substitute for S(+)-amphetamine. The three-lever drug discrimination procedure may provide a more sensitive behavioral assay in which to examine the discriminative stimulus effects of drugs with compound stimulus properties.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
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- Transient reinforcing effects of phenylisopropylamine and indolealkylamine hallucinogens in rhesus monkeys Behavioural Pharmacology March 1, 2004
- A three-choice discrimination procedure dissociates the discriminative stimulus effects of d-amphetamine and (±)-MDMA in rats. Experimental and Clinical Psychopharmacology 2000
- Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy Journal of Psychopharmacology September 10, 2020
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Cites 16
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- Stereochemical effects of 3,4-methylenedioxymethamphetamine (MDMA) and related amphetamine derivatives on inhibition of uptake of [3H]monoamines into synaptosomes from different regions of rat brain. Biochemical Pharmacology July 15, 1987
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- Assessment of the discriminative stimulus effects of the optical isomers of ecstasy (3,4-methylenedioxymethamphetamine; MDMA) Behavioural Pharmacology April 1, 1995
- Discriminative stimulus effects of the optical isomers of 3,4-methylenedioxyamphetamine (MDA) Behavioural Pharmacology October 1, 1992
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