AGE MODULATES THE LONG-TERM BUT NOT THE ACUTE EFFECTS OF THE SEROTONERGIC NEUROTOXICANT 3,4-METHYLENEDIOXYMETHAMPHETAMINE

Tissue levels of serotonin (5-HT), levels of its metabolite 5-hydroxyi ndoleacetic acid (5-HIAA) and populations of 5-HT reuptake sites were measured in the brains of rats exposed to 3,4-methylenedioxymethamphet amine (MDMA) at selected developmental ages. MDMA exposure at postnata l day (PND) 10 did not result in altered 5-HT or 5-HIAA levels 1 week after administration in any brain region examined. However, MDMA expos ure at PND 40 and PND 70 resulted in dose-dependent reductions in 5-HT and 5-HIAA levels at 1 week in all brain regions examined. Time cours e studies revealed that at PND 10, MDMA acutely (less than or equal to 24 hr) reduced 5-HT levels and that these levels later recovered to c ontrol levels. MDMA also acutely reduced 5-HT levels at PND 40 and PND 70, but at these ages the 5-HT levels were persistently depressed (gr eater than or equal to 72 hr). Time course studies also revealed that MDMA acutely elevated dopamine levels in caudate putamen at PND 40 and PND 70, but no alterations in dopamine levels were observed at PND 10 . Analysis of 5-HT reuptake site populations revealed that at PND 10 a nd PND 40, MDMA had little effect on reuptake site populations. At PND 70, however, MDMA reduced 5-HT reuptake site populations as early as 24 hr after administration. These experiments demonstrate not only tha t the biochemical effects of MDMA exposure are altered by the developm ental status of the experimental animal, but also that each individual biochemical component may show differing sensitivities to alteration by MDMA at different developmental ages.