Effects of valproate, phenytoin, and MK-801 in a novel model of epileptogenesis

Epilepsia
C D ApplegateK Ozduman

Abstract

We have developed and characterized a novel model of epileptogenesis based on the convulsive actions of flurothyl in mice. The hallmark feature of this model is a reliable change in the type of seizure expressed in response to flurothyl from generalized clonic to generalized tonic seizures. The purpose of our study was to evaluate the effects of chronic administration of valproate (VPA), phenytoin (PHT), and MK-801 on the change in seizure phenotype observed in our model system. Male C57BL/6J mice received flurothyl seizures on 8 consecutive days. Two hours after the last generalized seizure, chronic drug or vehicle was administered twice daily at 12-h intervals for 28 days. The drugs evaluated were VPA (250 mg/kg), PHT (30 mg/kg), and MK-801 (0.5 mg/kg). After a 7-day drug washout period, mice were retested with flurothyl. Among uninjected or vehicle-injected control mice, there was a significant increase in the proportion of animals expressing tonic seizures after the 28-day stimulation-free interval. Chronic administration of VPA or MK-801, but not PHT, blocked the characteristic change in seizure type from clonic to tonic. The change in seizure phenotype observed after exposure to our paradigm indicates a fundamental reorga...Continue Reading

References

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Citations

Apr 2, 2003·Pharmacology, Biochemistry, and Behavior·Yasuhiko HashimotoYutaka Gomita
Dec 19, 1998·Neuroreport·R J Ferland, C D Applegate
Jul 24, 2001·Drugs·N R TemkinG D Anderson
Oct 3, 1999·Journal of Neurosurgery·N R TemkinH R Winn
Aug 9, 2006·Expert Review of Neurotherapeutics·Carlo Alberto Pagni, Francesco Zenga
Mar 19, 2014·ACS Chemical Biology·John GilchristFrank Bosmans
Jul 13, 2007·Epilepsy Research·Francesco MarrosuGiampaolo Mereu
Feb 1, 2015·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Ben A ChindoAxel Becker
Sep 12, 2009·Epilepsy Research·Dominick PapandreaRussell J Ferland
Jul 28, 2017·Bio-protocol·Russell J Ferland
Jun 15, 2021·Frontiers in Neurology·Mohamed KhatebMoshe Herskovitz

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