Increased neuronal nitric oxide synthase (nNOS) activity triggers picrotoxin-induced seizures in rats and evidence for participation of nNOS mechanism in the action of antiepileptic drugs

Karthik Rajasekaran, Rajadas Jayakumar, Kalyamurthy Venkatachalam

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Increased neuronal nitric oxide synthase (nNOS) activity was observed during the prodromal period of seizures in various rat brain regions following administration of GABAA receptor antagonist, picrotoxin (PCT). Pretreatment with the selective nNOS inhibitor 7-nitroindazole (7-NI), dose- and time-dependently delayed the onset of clonus with a corresponding decrease in nNOS activity. The threshold dose of antiepileptic drugs (AEDs; diazepam, phenobarbitone and gabapentin) have potentiated the anticonvulsant action by pretreatment with graded doses of 7-NI. The increase in efficacy of anticonvulsant action correlated with a corresponding decrease of PCT-evoked increase in nNOS activity. The present data support a role for abnormal nNOS activity in mechanisms that trigger seizures and suggest a possible NO-mediated interplay between GABAA and glutamate receptors. The results of the present study provide evidence for a trigger role of neuronally produced NO in epileptogenesis induced by PCT and the participation of nNOS inhibitory mechanisms in the action of AEDs.

Original languageEnglish (US)
Pages (from-to)85-97
Number of pages13
JournalBrain Research
Volume979
Issue number1-2
DOIs
StatePublished - Jul 25 2003

Keywords

  • Antiepileptic drug
  • Epilepsy
  • Neuronal oxide synthase
  • Nitric oxide
  • Picrotoxin
  • Seizure

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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