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

Abstract Using in situ hybridization and immunohistochemical techniques, we examined the expression pattern of egr-1 mRNA and Egr-1 protein in several brain regions following administration of 3,4-methylenedioxymethamphetamine (MDMA). Furthermore, we also studied the role of N -methyl- d -aspartate (NMDA) receptor, dopamine D 1 receptor, 5-hydroxytryptamine (5-HT) transporter or 5-HT 2A receptor in the induction of egr-1 mRNA by MDMA. Basal constitutive levels of egr-1 mRNA were detected in control rat brains. A single administration of MDMA (10 mg/kg) caused marked induction of egr-1 mRNA in the prefrontal cortex, striatum and hippocampal dentate gyrus. However, no changes in the egr-1 mRNA levels were detected in the CA1 region of hippocampus and occipital cortex after administration of MDMA (10 mg/kg). Furthermore, the expression of egr-1 mRNA in the prefrontal cortex, striatum and hippocampal dentate gyrus after administration of MDMA (10 mg/kg) was blocked significantly 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), dopamine D 1 receptor antagonist SCH 23390 (1 mg/kg) or 5-HT uptake inhibitor paroxetine (5 mg/kg), but not by 5-HT 2A receptor antagonist SR46349B (5 mg/kg). However, high basal levels of Egr-1 immunoreactivity in the rat brain were 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 brain, 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.