title: Prophylactic, prandial rofecoxib treatment lacks efficacy against acute PTZ-induced seizure generation and kindling acquisition.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neuroscience, University of Connecticut School of Medicine, Farmington, Connecticut 06030-3401, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Claycomb
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Hewett
authors.forename: James A
authors.initials: JA
authors.lastname: Hewett
mesh_terms: D000818:Animals; D000927:Anticonvulsants; D001522:Behavior, Animal / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D003292:Convulsants; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004435:Eating; D005108:Extinction, Psychological / Q000187:drug effects; D018565:Food-Drug Interactions; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000494:pharmacology; D007696:Kindling, Neurologic / Q000187:drug effects*; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D013450:Sulfones / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D003292:Convulsants; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D051546:Cyclooxygenase 2; D007608:Kainic Acid; D010433:Pentylenetetrazole