3,4-Methylenedioxymethamphetamine (MDMA, ecstasy)-induced egr-1 mRNA in rat brain: pharmacological manipulation

Using in situ hybridization and immunohistochemical techniques, we examined the expression pattern of egr-1 mRNA and Egr-1 protein in several brain re gions following administration of 3,4-methylenedioxymethamphetamine (MDMA). Furthermore, we also studied the role of N-methyl-D-aspartate (NMDA) recep tor, dopamine D-1 receptor, 5-hydroxytryptamine (5-HT) transporter or 5-HT2 A receptor in the induction of egr-1 mRNA by MDMA. Basal constitutive level s of egr-1 mRNA were detected in control rat brains. A single administratio n of MDMA (10 mg/kg) caused marked induction of egr-1 mRNA in the prefronta l cortex, striatum and hippocampal dentate gyrus. However, no changes in th e egr-1 mRNA levels were detected in the CA1 region of hippocampus and occi pital cortex after administration of MDMA (10 mg/kg). Furthermore, the expr ession of egr-1 mRNA in the prefrontal cortex, striatum and hippocampal den tate gyrus after administration of MDMA. (10 mg/kg) was blocked significant ly by pretreatment with NMDA receptor antagonist (5R,10S)-(+)5-methyl-10,11 -dihydro-5H-dibenzo[a,b]-cyclohepten-5,10-imine ((+)-MK801; 1 mg/kg), dopam ine D-1 receptor antagonist SCH 23390 (1 mg/kg) or 5-HT uptake inhibitor pa roxetine (5 mg/kg), but not by 5-HT2A receptor antagonist SR46349B (5 mg/kg ). However, high basal levels of Egr-1 immunoreactivity in the rat brain we re not altered by administration of MDMA (10 mg/kg). These results suggest that MDMA alters the expression of egr-1 mRNA in several regions of rat bra in, and that the expression of egr-1 mRNA by MDMA in the prefrontal cortex, striatum and hippocampal dentate gyrus appears to be mediated, at least in part, by NMDA receptor, dopamine D-1 receptor and 5-HT transporter. (C) 20 00 Elsevier Science B.V. All rights reserved.