Date of Award
Doctor of Philosophy
(±)3,4-Methylenedioxymethamphetamine (MDMA) is a common drug of abuse known as "ecstasy." Currently, MDMA is classified into the traditional drug classes as both a "stimulant" and a "hallucinogen" because it is reported to share both subjective and physiological properties of both classes. MDMA is thought to produce its psychoactive effects by acting as both a serotonin and a dopamine agonist. However, the relative importance of the serotonin and dopamine neurotransmitter systems in mediating the stimulus properties of MDMA remains unclear.
The drug discrimination assay is used to classify drugs as "similar" or "dissimilar," as well as to examine underlying neurochemical changes associated with the stimulus properties of psychoactive compounds. Two-lever drug discriminations comparing the stimulus properties of MDMA to other psychostimulants and hallucinogens have produced conflicting reports. However, Goodwin and Baker (2000) established that rats could be successfully trained to discriminate damphetamine, a dopamine agonist, and MDMA from saline in a three-lever drug discrimination procedure. The present study sought to train 12 rats to discriminate (+)-lysergic acid diethylamide (LSD), a serotonin agonist, and MDMA from saline in a similar three-lever procedure.
All subjects acquired the discrimination, though it appears the stimulus effects of LSD and MDMA are difficult to distinguish. This is evidenced by the difficulties establishing and demonstrating maintenance of the discrimination in the beginning stages of the study. Overall, subjects required an average of 153 training sessions in order to demonstrate adequate stimulus control.
d-Amphetamine produced only partial substitution for MDMA while the serotonin releaser, fenfluramine, did completely substitute for MDMA. Low doses of both d-amphetamine and fenfluramine given in combination substituted for MDMA at only one of the combinations. Moreover, the serotonin antagonist MDL- 100907 only partially blocked the MDMA cue while the dopamine antagonist haloperidol did not produce any decrease in MDMA responding. Conversely, MDL- 100907 did completely block the LSD cue.
Taken together, these results support the notion that the stimulus effects of MDMA are clearly different from those of other psychostimulants and hallucinogens, and should therefore be classified into a distinct drug class. Indeed, Nichols (1986) has proposed that MDMA and similar amphetamine analogs belong in a separate drug class, for which he has coined the term "entactogens." It also is evident that whether animals are trained to discriminate MDMA from d-amphetamine or from LSD, serotonin release is a salient feature of MDMA discrimination.
Goodwin, Amy K., "Assessment N>e Discriminative Stimulus Effects of (±)-3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") and (+Lysergic Add Diethylamide (LSD) in a Three-Lever Drug Discrimination Procedure" (2002). Dissertations. 1277.