Effects of MK-801 and phenytoin on flurothyl-induced seizures during development.
We determined the effects of the N-methyl-D-aspartate (NMDA) receptor blocker MK-801 (0.05, 0.1, and 0.5 mg/kg intraperitoneally, i.p.) and phenytoin (PHT, 5, 10, and 20 mg/kg i.p.) on flurothyl-induced clonic and tonic-clonic seizures in 9-, 15-, 30-, and 60-day-old male rats. Both agents had seizure-, age-, and dose-specific effects. The highest dose of MK-801 was anticonvulsant against clonic flurothyl-induced seizures only in 9- and 60-day-old rats, but suppressed tonic-clonic seizures in all ages. The lowest dose of MK-801 (0.05 mg/kg) produced significant anticonvulsant effects only in 15 day old rats. PHT did not have any effect on clonic seizures throughout development. Both doses of PHT (10 and 20 mg/kg) were anticonvulsant against tonic-clonic seizures in adult rats but not in any other age group. The results indicate that NMDA receptors play an important role in tonic-clonic flurothyl-induced seizures throughout development (especially in 15-day-old rats) and that the anticonvulsant effects of PHT may vary at different stages of brain development.
Velísek
L
L
Department of Neurology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461.
Velísková
J
J
Ptachewich
Y
Y
Shinnar
S
S
Moshé
S L
SL
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced / Q000517:prevention & control; D005481:Flurothyl / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D010672:Phenytoin / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control*
D016194:Receptors, N-Methyl-D-Aspartate; D010672:Phenytoin; D016291:Dizocilpine Maleate; D005481:Flurothyl