Discriminative stimulus effects of the optical isomers of 3,4-methylenedioxyamphetamine (MDA)

In rats trained to distinguish either the left- or right-handed form (isomer) of the drug MDA from saline, both isomers served as reliable cues at specific doses. The two isomers substituted for each other, and both were fully substituted by the related drug MDMA. The hallucinogens LSD and DOM substituted only for the left-handed isomer, while stimulants like amphetamine and cocaine did not produce MDA-like effects. The left-handed isomer's cue was blocked by a serotonin receptor antagonist, but dopamine blockers had no effect. Neither MDA isomer fully substituted for LSD or amphetamine cues, suggesting the left-handed isomer has more hallucinogen-like and serotonin-mediated effects, while both lack strong amphetamine-like properties.

Study at a glance

Abstract

The isomers of 3,4-methylenedioxyamphetamine (MDA) functioned as discriminative stimuli in rats trained to discriminate either (-) MDA (1.25mg/kg) or (+) MDA (1.25mg/kg) from saline. Dose- and time-response curves indicated that drug lever selection occurred at doses of at least 1.00mg/kg of (-) MDA and 0.75mg/kg of (+) MDA and that drug-appropriate responding for both isomers was maintained for at least 90min. Cross-substitution was observed between the MDA isomers; both (+) and (-) 3,4-methylenedioxymethamphetamine (MDMA) also substituted completely for (+) and (-) MDA. The hallucinogens (+)-lysergic acid diethylamide (LSD) and (+/-)-2,5-dimethoxy-4-methylamphetamine (DOM), substituted for (-) MDA; neither mescaline nor (+) amphetamine or cocaine had (-) MDA-like effects. LSD also substituted for (+) MDA; DOM, mescaline, (+) amphetamine and cocaine failed to have (+) MDA-like effects. The (-) but not the (+) MDA cue was blocked by the 5-HT(2) antagonist pirenpirone; the dopamine (DA) antagonists SCH-23390 and (-) sulpiride had no effect on either the (-) or (+) MDA cues. When animals were trained to discriminate LSD (0.16mg/kg) or (+) amphetamine (1.0mg/kg) from saline, neither (-) MDA nor (+) MDA substituted completely. These results indicate that: (1) the stimulus effects of the isomers of MDA and MDMA are similar; (2) (-) MDA may be more hallucinogenic (or more accurately, LSD- or DOM-like) than (+) MDA; (3) neither (+) nor (-) MDA has potent amphetamine-like effects; and (4) the effects of (-) MDA may be more serotonergic than those of (+) MDA.