Prophylactic, prandial rofecoxib treatment lacks efficacy against acute PTZ-induced seizure generation and kindling acquisition

Robert J. Claycomb, Sandra J. Hewett, James A. Hewett

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Purpose: The goal of this study was to determine whether prophylactic prandial administration of rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, could alter seizure generation, kindling acquisition, and/or kindling maintenance in the mouse pentylenetetrazole (PTZ) epilepsy model. Methods: Male CD-1 mice were fed ad libitum with control chow or chow formulated to deliver 30 mg/kg/day rofecoxib. After 5 days, mice were treated with a single dose of 40 or 55 mg/kg PTZ (acute paradigm) or 40 mg/kg PTZ delivered daily (kindling paradigm). Seizure severity was scored on a four-point behavioral scale and COX-2 expression was assessed in brain slices from a subset of mice 3 h or 72 h after acute PTZ or following establishment of kindling. Key Findings: Hippocampal COX-2 expression was transiently upregulated 3 h after an acute PTZ-induced convulsion and returned to baseline levels within 72 h, whereas it remained elevated for at least 72 h after the final seizure in the kindling paradigm. Despite this increase, chronic rofecoxib treatment did not attenuate the severity of acute PTZ-induced seizures and failed to alter kindling development or maintenance. Significance: The present study demonstrates that prophylactic, prandial rofecoxib treatment lacks efficacy against acute PTZ-induced seizure generation and kindling acquisition, and does not reverse the kindled state once established.

Original languageEnglish (US)
Pages (from-to)273-283
Number of pages11
JournalEpilepsia
Volume52
Issue number2
DOIs
StatePublished - Feb 2011

Keywords

  • Cyclooxgenase-2
  • Epilepsy
  • Epileptogenesis
  • Kindling
  • Pentylenetetrazole
  • Seizures

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Prophylactic, prandial rofecoxib treatment lacks efficacy against acute PTZ-induced seizure generation and kindling acquisition'. Together they form a unique fingerprint.

  • Cite this