Estimating the relative reinforcing strength of (+/-)-3,4-methylenedioxymethamphetamine (MDMA) and its isomers in rhesus monkeys: comparison to (+)-methamphetamine
by
Wang Z, Woolverton WL.
Department of Psychiatry, University of Mississippi Medical Center,
2500 N. State Street, Jackson, MS, 39216, USA,
Wwoolverton@psychiatry.umsmed.edu.
Psychopharmacology (Berl). 2006 Oct 25;

ABSTRACT

RATIONALE: (+/-)3,4-Methylenedioxymethamphetamine (MDMA) is an analog of methamphetamine (MA) and a drug of abuse. MA, MDMA, and its isomers release monoamine neurotransmitters with varying selectivities and would, therefore, be predicted to vary in their relative strength as reinforcers. OBJECTIVES: This study compared self-administration of MA, MDMA, and its isomers using a progressive-ratio schedule in rhesus monkeys. METHODS: Rhesus monkeys [n = 6, MA and MDMA; n = 5, (+)-MDMA and (-)-MDMA] were prepared with chronic i.v. catheters and allowed to self-administer cocaine or saline in daily baseline sessions. When responding was stable, MA (0.006-0.1 mg/kg per injection), MDMA (0.025-0.8 mg/kg injection), (+)-MDMA (0.025-0.8 mg/kg per injection), or (-)-MDMA (0.05-0.8 mg/kg per injection) was made available in test sessions. RESULTS: MA, MDMA, and (+)-MDMA functioned as positive reinforcers in all monkeys with a potency relationship of MA > (+)-MDMA > (+/-)-MDMA. Two of five monkeys took (-)-MDMA above saline levels. Dose-response relationships were biphasic for MA and (+/-)-MDMA, and asymptotic for (+)-MDMA. In terms of maximum number of injection per session, a measure of relative reinforcing strength, the order was MA > (+)-MDMA = (+/-)-MDMA > (-)-MDMA. CONCLUSIONS: MDMA and (+)-MDMA were consistent positive reinforcers, but weaker than MA, whereas (-)-MDMA was, at best, a weak reinforcer in some monkeys. The reinforcing strength of MDMA appears to derive primarily from (+)-MDMA. Because MDMA and its isomers have been shown to have relatively higher serotonin to dopamine releasing potency, these data support the hypothesis that increasing 5-HT releasing potency relative to DA is associated with weaker reinforcing effects.

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