The effects of a neurotoxic regimen of MDMA on neonatal rats exposed between postnatal days 1 to 4. Rats in this study received 10 mg/kg MDMA injected twice daily for 4 days. Since previous studies suggested that neonatal rats did not become hyperthermic after MDMA, and did not show any signs of serotonergic neurotoxicity after exposure, the authors either exposed rats to high (37 C) or less high (31 C) temperature during MDMA exposure. Rats were sacrificed either at postnatal day 25 or day 60 (21 or 56 days after the final dose of MDMA), and brain neurotransmitter content was examined via HPLC. Serotonin transporter (SERT) was measured via radioactively labeled paroxetine. (Two rats were sacrificed at Day 5 to examine signs of apoptotic activity). Hippocampal serotonin (5-HT) content was lower in MDMA treated neonatal rats regardless of ambient temperature; values for the 5-HT metabolite 5-HIAA were lower, but not significantly so. This was true at postnatal day 25 and 60. Hippocampal values for homovanillic acid (HVA), a dopamine metabolite, did decline after high versus low ambient temperature. Hippocampal SERT levels at postnatal day 25 had also declined after MDMA treatment. Differences in hippocampal SERT remained at postnatal day 60, and in addition, neocortex SERT binding was lower in MDMA treated rats. Study findings indicate that MDMA can produce serotonergic neurotoxicity in neonatal rats, independent of degree of presumed hyperthermia. It appears that early exposure to MDMA (equivalent to exposure in the last trimester of pregnancy in humans) might affect serotonin in hippocampus, and these effects may harm projections to the neocortex appearing after the initial exposure. These findings can be contrasted with findings a study of cultured fetal mouse neurons (Won et al. 2002) that seems to suggest an increase in growth and activity in serotonin neurons taken from fetuses exposed to MDMA in utero.