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-hydroxyindoleacetic acid (5-HIAA) and populations of 5-HT reuptake sites were measured in the brains of rats exposed to 3,4-methylenedioxymethamphetamine (MDMA) at selected developmental ages. MDMA exposure at postnatal 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 exposure 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 course studies revealed that at PND 10, MDMA acutely (< or = 24 hr) reduced 5-HT levels and that these levels later recovered to control 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 ( > or = 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 and 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 that the biochemical effects of MDMA exposure are altered by the developmental status of the experimental animal, but also that each individual biochemical component may show differing sensitivities to alteration by MDMA at different developmental ages.
Interdisciplinary Toxicology Program, University of Arkansas for Medical Sciences, Little Rock.
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Broening
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Bacon
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Slikker
D000367:Age Factors; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000032:analysis* / Q000378:metabolism
D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine