Article
Role of dopamine transporters in the behavioral effects of 3,4-methylenedioxymethamphetamine (MDMA) in nonhuman primates
Psychopharmacology (Berl).
(2009)
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.
Keywords
- MDMA,
- PET neuroimaging,
- Microdialysis,
- Dopamine,
- Serotonin,
- Operant behavior Nonhuman primates
Disciplines
Publication Date
August, 2009
DOI
10.1007/s00213-009-1545-0
Citation Information
William E. Fantegrossi, Rayna M. Bauzo, Daniel F. Manvich, Jose C. Morales, et al.. "Role of dopamine transporters in the behavioral effects of 3,4-methylenedioxymethamphetamine (MDMA) in nonhuman primates" Psychopharmacology (Berl). Vol. 205 Iss. 2 (2009) p. 337 - 347 ISSN: 1432-2072 Available at: http://works.bepress.com/daniel-manvich/13/