Non-competitive NMDA receptor antagonists moderate seizure-induced c-fos expression in the rat cerebral cortex.
We examined the effects of non-competitive NMDA glutamate receptor antagonists on seizures elicited by 4-aminopyridine (4-AP), and in particular, on the expression of the transcription factor c-fos induced by these seizures. Induction of c-fos mRNA due to 4-AP-elicited seizures was ascertained by reverse transcription polymerase chain reaction in samples of the neocortex. Adult rats were pretreated with the NMDA receptor antagonists amantadine (40 mg/kg), ketamine (3mg/kg), dizocilpine (MK-801; 1mg/kg) or dextrometorphan (40 mg/kg); 4-AP (5mg/kg) was then injected i.p. Controls were treated with either antagonist only or with 4-AP only. Pretreatment with the antagonists (with the exception of amantadine) increased the latency of behavioural seizures, but not all of the antagonists caused symptomatic seizure protection. In the brains which were processed for Fos immunohistochemistry, quantitative evaluation of immunostained cells was performed in the neocortex and hippocampus. Treatment with either antagonist did not induce by itself c-fos expression, with the exception of amantadine, which caused slight Fos induction in the neocortex. Pretreatment with all the antagonists resulted in decrease of seizure-induced Fos immunoreactivity with respect to non-pretreated animals. Decrease of immunostained cells was significant in the neocortex, in the granule cell layer and hilus of the dentate gyrus, in hippocampal areas CA1 and CA2. MK-801, ketamine and dextrometorphan decreased significantly Fos immunoreactivity also in area CA3. The decrease of Fos immunostaining was not directly correlated with a suppression of behavioural seizures. The results support an important role of NMDA receptors in c-fos gene induction in acute 4-AP seizures.
Szakács
Réka
R
Department of Psychiatry, Faculty of Medicine, University of Szeged, Szeged, Hungary.
Weiczner
Roland
R
Mihály
András
A
Krisztin-Péva
Beáta
B
Zádor
Zsolt
Z
Zádor
Erno
E
D015761:4-Aminopyridine / Q000494:pharmacology; D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002540:Cerebral Cortex / Q000737:chemistry / Q000503:physiopathology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D015870:Gene Expression; D006624:Hippocampus / Q000737:chemistry / Q000503:physiopathology*; D007150:Immunohistochemistry; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D026902:Potassium Channel Blockers; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; D000547:Amantadine; D015761:4-Aminopyridine