Pentylenetetrazol (PTZ) Kindling Model of Epilepsy

Ashish Dhir1

1 Department of Neurology, School of Medicine, University of California Davis Medical Center, Sacramento, California
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 9.37
DOI:  10.1002/0471142301.ns0937s58
Online Posting Date:  January, 2012
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Abstract

This unit describes a protocol to perform chemical kindling in mice. Kindling is a chronic animal model of epilepsy that has been extensively studied to understand the process of epileptogenesis and discover novel anti‐epileptic compounds. Kindling is a phenomenon where a sub‐convulsive stimulus (either chemical or electrical), if applied repetitively and intermittently, will ultimately lead to the generation of full‐blown convulsions. Kindling can be induced either by (1) electrical stimulation of different brain regions (electrical kindling) or (2) using various chemical agents (chemical kindling). This unit discusses in detail the methodology to execute pentylenetetrazol (PTZ; a GABAA receptor antagonist)–induced chemical kindling in mice. PTZ is administered chronically at a sub‐convulsive dose for a number of days. Seizure score is calculated after each PTZ injection. The effect of test/reference compounds can be tested by administering them either prior to the initiation of kindling (pre‐kindling phase) or after animals are fully kindled (post‐kindling phase). Curr. Protoc. Neurosci. 58:9.37.1‐9.37.12. © 2012 by John Wiley & Sons, Inc.

Keywords: epilepsy; chemical kindling; mice; pentylenetetrazol

     
 
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Table of Contents

  • Introduction
  • Strategic Planning
  • Basic Protocol 1: Establishing, Evaluating, and Utilizing a Mouse Model of PTZ‐Induced Kindling
  • Reagents and Solutions
  • Commentary
  • Literature Cited
  • Figures
     
 
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Materials

Basic Protocol 1: Establishing, Evaluating, and Utilizing a Mouse Model of PTZ‐Induced Kindling

  Materials
  • Male Swiss mice, 22 to 30 g
  • Mouse food and water
  • Pentylenetetrazol solution (35 mg/kg or 3.5 mg/ml, dose volume 10 ml/kg; see recipe)
  • Test/reference solution and vehicles (see recipe)
  • 0.9% (w/v) saline
  • Observation cages (transparent Plexiglass cages) with bedding material (16.5 × 10.5 × 7.5–in.3)
  • 1‐ml syringes and 25‐G needles
  • Personal protective equipments (laboratory coats, gloves, shoe covers, goggles)
  • Carbon dioxide euthanasia chamber
  • Microsoft Excel or any calculating software
  • Statistical analysis software
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Figures

Videos

Literature Cited

Literature Cited
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   Corda, M.G., Giorgi, O., Longoni, B., Orlandi, M., and Biggio, G. 1990. Decrease in the function of the gamma‐aminobutyric acid‐coupled chloride channel produced by the repeated administration of pentylenetetrazol to rats. J. Neurochem. 55:1216‐1221.
   da Silva, L.F., Pereira, P., and Elisabetsky, E. 1998. A neuropharmacological analysis of PTZ‐induced kindling in mice. Gen. Pharmacol. 31:47‐50.
   De Deyn, P.P., D'Hooge, R., Marescau, B., and Pei, Y.Q. 1992. Chemical models of epilepsy with some reference to their applicability in the development of anticonvulsants. Epilepsy Res. 12:87‐110.
   Dhir, A., Naidu, P.S., and Kulkarni, S.K. 2006. Effect of cyclooxygenase inhibitors on pentylenetetrazol (PTZ)‐induced convulsions: Possible mechanism of action. Prog. Neuropsychopharmacol. Biol. Psychiatry 30:1478‐1485.
   Dhir, A., Naidu, P.S., and Kulkarni, S.K. 2007. Neuroprotective effect of nimesulide, a preferential COX‐2 inhibitor, against pentylenetetrazol (PTZ)‐induced chemical kindling and associated biochemical parameters in mice. Seizure 16:691‐697.
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