3,4-Methylenedioxymethamphetamine administration on postnatal day 11 in rats increases pituitary-adrenal output and reduces striatal and hippocampal serotonin without altering SERT activity

Abstract We have previously shown that ±3,4-methylenedioxymethamphetamine (MDMA) treatment from P11 to P20 in rats produces deficits in cognitive ability when these animals are tested in adulthood. The purpose of this experiment was to explore the neuroendocrine and neurochemical changes produced by MDMA treatment on P11. We examined monoamines in the hippocampus and striatum and the serotonin transporter in the hippocampus as well as pituitary and adrenal output following administration of MDMA (10 mg/kg, 4 times) on postnatal day 11. Significant depletions in serotonin were evident in the hippocampus 1 h and in the striatum 24 h after the first dose and remained reduced 78 h later. No changes in serotonin transporter were observed following MDMA treatment, although females had lower levels than males. No changes in dopamine were detected. The metabolites of serotonin and dopamine had different profiles than the parent compounds after MDMA administration. Plasmatic ACTH was elevated immediately following MDMA and remained elevated for at least 1 h after the last dose and returned to baseline by 24 h. Corticosterone was increased after the first dose and remained increased for at least 24 h, and returned to baseline by 30 h. The decreases in serotonin in regions important for learning and memory in conjunction with elevated levels of corticosterone during a period of stress hyporesponsiveness suggest that these initial responses to MDMA may contribute to the long-term learning and memory deficits following neonatal MDMA exposure.