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 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.
Shirayama
Y
Y
Division of Cortical Function Disorders, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Kodaira, Japan. yukihiko.shirayama@yale.edu
Hashimoto
K
K
Iyo
M
M
Watanabe
K
K
Higuchi
T
T
Minabe
Y
Y
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D051766:Early Growth Response Protein 1; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005464:Fluorobenzenes / Q000494:pharmacology; D006213:Hallucinogens / Q000494:pharmacology*; D017874:Immediate-Early Proteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D017374:Paroxetine / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis*
D001552:Benzazepines; D004268:DNA-Binding Proteins; D016291:Dizocilpine Maleate; D018492:Dopamine Antagonists; D051766:Early Growth Response Protein 1; D018691:Excitatory Amino Acid Antagonists; D005464:Fluorobenzenes; D006213:Hallucinogens; D017874:Immediate-Early Proteins; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D017374:Paroxetine; D010636:Phenols; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D014157:Transcription Factors; C486110:Egr1 protein, rat; C076033:SR 46349B