Effect of lamotrigine, oxcarbazepine and topiramate on cognitive functions and oxidative stress in PTZ-kindled mice

Seizure. 2011 Apr;20(3):257-62. doi: 10.1016/j.seizure.2010.12.006. Epub 2011 Jan 17.

Abstract

Cognitive impairment is frequently observed in epileptic patients. It has been seen that not only epilepsy but antiepileptic drugs also impair cognitive functions. The present study was undertaken to assess the effect of three anticonvulsants viz. lamotrigine (5mg/kg, p.o.), oxcarbazepine (15mg/kg, p.o.) and topiramate (10mg/kg, p.o.) on cognitive function and oxidative stress during pentylenetetrazole (PTZ)-kindling in mice. Kindling was induced by the administration of PTZ (25mg/kg, i.p.) on every alternate day till 5 weeks. Cognition was assessed after the development of kindling. Elevated plus maze (EPM) and passive avoidance response (PAR) tests were carried out after 24h and 48h of the last PTZ administration. After completion of behavioural tests malondialdehyde (MDA), glutathione levels, superoxide dismutase and catalase activity were measured as an indicator of oxidative stress. The results of the present study indicate that topiramate (10mg/kg) administration to kindled animals increased transfer latency and decreased step-down latency in EPM and PAR tests, respectively. However, lamotrigine and oxcarbazepine did not alter the two parameters. Topiramate administration to kindled as well as non-kindled animals has shown increase in MDA and decrease in glutathione levels. Lamotrigine and oxcarbazepine did not show significant alteration in oxidative stress parameters. To conclude, long term administration of topiramate impairs cognitive functions during experimental epilepsy while lamotrigine and oxcarbazepine are safer.

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Carbamazepine / analogs & derivatives
  • Carbamazepine / pharmacology
  • Catalase / metabolism
  • Cognition Disorders* / drug therapy
  • Cognition Disorders* / etiology
  • Disease Models, Animal
  • Drug Interactions
  • Escape Reaction / drug effects
  • Fructose / analogs & derivatives
  • Fructose / pharmacology
  • Glutathione / metabolism
  • Kindling, Neurologic / drug effects*
  • Lamotrigine
  • Male
  • Malondialdehyde / metabolism
  • Maze Learning / drug effects
  • Mice
  • Oxcarbazepine
  • Oxidative Stress / drug effects*
  • Pentylenetetrazole / adverse effects*
  • Seizures* / chemically induced
  • Seizures* / complications
  • Seizures* / drug therapy
  • Superoxide Dismutase / metabolism
  • Topiramate
  • Triazines / pharmacology

Substances

  • Anticonvulsants
  • Triazines
  • Topiramate
  • Fructose
  • Carbamazepine
  • Malondialdehyde
  • Catalase
  • Superoxide Dismutase
  • Glutathione
  • Lamotrigine
  • Oxcarbazepine
  • Pentylenetetrazole