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Role of dopamine transporters in the behavioral effects of 3,4-methylenedioxymethamphetamine (MDMA)

Role of dopamine transporters in the behavioral effects of 3,4-methylenedioxymethamphetamine (MDMA)

  1. ThirdEyeFloond
    Psychopharmacology (Berl). 2009 May 7. [Epub ahead of print]

    Fantegrossi WE, Bauzo RM, Manvich DM, Morales JC, Votaw JR, Goodman MM, Howell LL.

    RATIONALE: The interoceptive and reinforcing effects of 3,4-methylenedioxymethamphetamine (MDMA) are similar to those of psychostimulants, but the role of dopamine in the behavioral effects of MDMA is not well documented, especially in primates. OBJECTIVE: The aim of this study was to assess the role of dopamine in the behavioral effects of MDMA in two nonhuman primate species. METHODS: The behavioral effects of MDMA, with and without serotonergic or dopaminergic pretreatments, were studied in squirrel monkeys trained to respond under a fixed-interval schedule of stimulus termination; effects on caudate dopamine levels were studied in a separate group of squirrel monkeys using in vivo microdialysis. Positron emission tomography neuroimaging with the dopamine transporter (DAT) ligand [(18)F]FECNT was used to determine DAT occupancy by MDMA in rhesus monkeys. RESULTS: MDMA (0.5-1.5 mg/kg) did not induce behavioral stimulant effects, but the highest dose of MDMA suppressed responding. Pretreatment with fluoxetine (3.0 mg/kg) or the selective 5HT(2A) antagonist M100907 (0.03-0.3 mg/kg) attenuated the rate suppressing effects of MDMA. In contrast, pretreatment with the selective dopamine transporter inhibitor RTI-177 (0.1 mg/kg) did not alter the rate suppressing effects of MDMA. Administration of MDMA at a dose that suppressed operant behavior had negligible effects on extracellular dopamine. The percent DAT occupancy of MDMA at a dose that suppressed operant behavior also was marginal and reflected low in vivo potency for DAT binding. CONCLUSIONS: Collectively, these results indicate that behaviorally relevant doses of MDMA do not induce behavioral stimulant or dopamine transporter-mediated effects in nonhuman primates.
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