Candidate: Amy K. Goodwin

Degree of: Doctor of Philosophy

Department: Psychology

Title: Assessment of the Discriminative Stimulus Effects of (+)-3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") and (+)-Lysergic Acid Diethylamide (LSD) in a Three-Lever Drug Discrimination Procedure

Date: Monday, May 20, 2002, 10:00 a.m. - 12:00 p.m., 3715 Wood Hall

Committee:
Dr. Lisa Baker, Chair
Dr. Lester Wright
Dr. Alan Poling
Dr. Kjell Svensson

Abstract:
(+)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. The two-lever drug discrimination literature 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 d-amphetamine, 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, as the number of sessions to acquire the discrimination averaged 153. Moreover, it appeared that the discrimination was not adequately maintained in the beginning stages of the study and subjects required additional training sessions in order to again meet and maintain the discrimination.

d-Amphetamine produced only partial substitution for MDMA in the present study. However, the serotonin releaser, fenfluramine, did completely substitute for MDMA. Low doses of both d-amphetamine and fenfluramine given in combination also failed to completely substitute for the MDMA cue. 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 tem "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.  

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