Role of Dopamine Transporters in the Behavioral Effects of 3,4-methylenedioxymethamphetamine (MDMA) in Nonhuman Primates

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2009 May 8

PMID 19421742

Citations 13

Authors

William E Fantegrossi

Rayna M Bauzo

Daniel M Manvich

Jose C Morales

John R Votaw

Mark M Goodman

Leonard L Howell

Affiliations

Soon will be listed here.

Abstract

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 [18F]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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