ORAL-ADMINISTRATION OF 3,4-METHYLENEDIOXYMETHAMPHETAMINE (MDMA) PRODUCES SELECTIVE SEROTONERGIC DEPLETION IN THE NONHUMAN PRIMATE

MDMA (3,4-methylenedioxymethamphetamine) has been reported to produce serotonergic depletion in nonhuman primates at doses as low as 2.5 mg/ kg (1-2 times the typical human dose). The current study evaluated the dose-response relationships of MDMA (1.25-20.0 mg/kg) using regional concentrations of serotonin (5-HT) and its metabolite, 5-hydroxyindole acetic acid (5-HIAA), and home cage behavior as endpoints. Adult femal e rhesus monkeys (n = 16) were treated orally with 0, 1.25, 2.5, or 20 .0 mg/kg MDMA twice daily for 4 consecutive days. Eighteen behaviors w ere measured in the home cage prior to, during, and after MDMA treatme nt. One month after the last dose, the animals were sacrificed and bra ins dissected into several regions for neurochemical analyses. 5-HT an d 5-HIAA were analyzed via HPLC/EC. The lower doses of MDMA (1.25 and 2.5 mg/kg) did not significantly alter 5-HT or 5-HIAA concentrations i n any brain region except hippocampus in which 5-HT concentrations wer e decreased after 2.5 mg/kg. MDMA at 20.0 mg/kg significantly decrease d 5-HT and 5-HIAA concentrations in several cortical and midbrain stru ctures. However, 5-HT and 5-HIAA concentrations in brain stem and hypo thalamus were not significantly altered after any dose of MDMA. Combin ed with previous data from this laboratory, these results indicate tha t the decreased concentrations of 5-HT and 5-HIAA in selected brain re gions show a selective dose-response relationship for MDMA-induced neu rotoxicity as measured by serotonergic depletion in the nonhuman prima te.