Citation

Goodwin AK, Mueller M, Shell CD, Ricaurte GA, Ator NA. J. Pharmacol. Exp. Ther. 2013; 345(3): 342-353.

Affiliation

Johns Hopkins University School of Medicine;

Copyright

(Copyright © 2013, American Society for Pharmacology and Experimental Therapeutics)

DOI

10.1124/jpet.113.203729

PMID

23516331

Abstract

(±)-3,4-Methylenedioxymethamphetamine HCl (MDMA, "Ecstasy") is a popular drug of abuse. We aimed to characterize the behavioral effects of intragastric MDMA in a species closely related to humans and to relate behavioral effects to plasma MDMA and metabolite concentrations. Single doses of MDMA (0.32 - 7.8 mg/kg) were administered via an intragastric catheter to adult male baboons (N=4). Effects of MDMA on food-maintained responding were assessed over a 20-h period, while untrained behaviors and fine-motor coordination were characterized every 30 min until 3 h post-administration. Levels of MDMA and metabolites in plasma were measured in the same animals (N=3) following dosing on a separate occasion. MDMA decreased food-maintained responding over the 20-h period, and systematic behavioral observations revealed increased frequency of bruxism as the dose of MDMA was increased. Drug blood level determinations showed no MDMA after the lower doses of MDMA tested (0.32-1.0 mg/kg) and modest levels following higher MDMA doses (3.2-7.8 mg/kg). High levels of 3,4-dihydroxymethamphetamine (HHMA) were detected after all doses of MDMA, suggesting extensive first-pass metabolism of MDMA in the baboon. The present results demonstrate that MDMA administered via an intragastric catheter produced behavioral effects that have also been reported in humans. Similar to humans, blood levels of MDMA following oral administration may not be predictive of the behavioral effects of MDMA. Metabolites, particularly HHMA, may play a significant role in the behavioral effects of MDMA.

Language: en