Serial day rapid kindling is an effective tool in screening the anti-epileptic properties of topiramate

Seizure. 2007 Oct;16(7):620-6. doi: 10.1016/j.seizure.2007.04.013. Epub 2007 Jun 7.

Abstract

Introduction: In this study, a serial day rapid kindling protocol was used to fully kindle rats in a matter of days. Subsequently, the anticonvulsant profile of a relatively new anti-epileptic drug, topiramate, was evaluated in a cross-over design to further validate this rapid kindling model.

Methods: Rats were kindled during three consecutive days, according to the serial day rapid kindling protocol. Topiramate was tested at a dose of 100mg/kg, i.p., over the next 2 days using a cross-over design. The stability of the kindled state was evaluated in all rats during two retest paradigms. During the drug-testing procedure, rats received a single i.p. injection of either topiramate or verhicle. Starting 1 h later the rats received additional kindling stimulations during which their response was measured.

Results: Serial day rapid kindling induced a long lasting and stable fully kindled state that allowed for the anti-epileptic drug screening procedure. Topiramate reduced both the afterdischarge duration and ameliorated seizure semiology in the kindled rats.

Discussion: Serial day rapid kindling provided a tool to rapidly kindle rats in 3 days. Using a cross-over design, clear indications on anti-epileptic activity of a given drug can be determined using few laboratory animals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / blood
  • Anticonvulsants / therapeutic use*
  • Electrodes, Implanted
  • Electroencephalography
  • Epilepsy / diagnosis*
  • Epilepsy / drug therapy*
  • Fructose / analogs & derivatives*
  • Fructose / blood
  • Fructose / therapeutic use
  • Hippocampus / physiopathology
  • Kindling, Neurologic / physiology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Recurrence
  • Reproducibility of Results
  • Seizures / physiopathology
  • Topiramate

Substances

  • Anticonvulsants
  • Topiramate
  • Fructose