Dissociation between Serotonin Neurotoxicity and Brain-Derived Neurotrophic Factor Induction following Neonatal MDMA Exposure in Rats

Abstract

Early developmental treatment of rats with 3,4-methylenedioxymethamphetamine (MDMA) was previously found to cause an abnormal pattern of forebrain serotonergic axon density in adulthood consisting of a cortical hypoinnervation and a striatal hyperinnervation. The present study tested the hypothesis that this reorganization was due to regional differences in brain-derived neurotrophic factor (BDNF) expression. Rats received MDMA (10 mg/kg, s.c., b.i.d.) on postnatal days (PD) 1–4, after which brain tissues were collected on PD 11, 30, and 67 for analysis. BDNF protein levels were found to be elevated in the occipital cortex but not in the hippocampus or striatum following MDMA administration. Serotonin transporter binding (an index of serotonergic fiber integrity) was significantly reduced in the hippocampus at PD 11 but returned to normal by PD 30, whereas the cortex exhibited a delayed reduction that was not manifested until PD 30. These results do not support the view that a region-specific enhancement in BDNF expression mediates the abnormal serotonergic reinnervation observed following neonatal MDMA exposure.