Behavioral Effects and Pharmacokinetics of (±)-3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy) after Intragastric Administration to Baboons

• Published in: The Journal of pharmacology and experimental therapeutics 2013-06, Vol.345 (3), p.342-353
• Main Authors: Goodwin, Amy K., Mueller, Melanie, Shell, Courtney D., Ricaurte, George A., Ator, Nancy A.
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal - drug effects; Behavioral Pharmacology; Biotransformation; Body Weight - physiology; Conditioning, Operant - drug effects; Dose-Response Relationship, Drug; Food; Hallucinogens - administration & dosage; Hallucinogens - pharmacokinetics; Hallucinogens - pharmacology; Intubation, Gastrointestinal; Male; Motor Skills - drug effects; N-Methyl-3,4-methylenedioxyamphetamine - administration & dosage; N-Methyl-3,4-methylenedioxyamphetamine - pharmacokinetics; N-Methyl-3,4-methylenedioxyamphetamine - pharmacology; Papio
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.113.203729

(±)-3,4-Methylenedioxymethamphetamine (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-hour period, whereas untrained behaviors and fine-motor coordination were characterized every 30 minutes until 3 hours postadministration. Levels of MDMA and metabolites in plasma were measured in the same animals (n = 3) after dosing on a separate occasion. MDMA decreased food-maintained responding over the 20-hour 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 after 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 after 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.