ACUTE HEAT-STRESS MODEL OF SEIZURES IN WEANLING RATS - INFLUENCE OF PROTOTYPIC ANTI-SEIZURE COMPOUNDS

The present study tested the therapeutic potential for prototype anti- epilepsy drugs using an animal model of infantile febrile seizures. Th e model consisted of immersion of weanling rats (21 days old) in a 45 degrees C water bath for a maximum of 4 min (four exposures over a 2 w eek period) and observing for the progression to stage-5 seizures. All compounds were administered orally at the respective ED,, for prevent ion of seizures in the maximal electroshock (MES) test. Clonazepam eff ectively lowered the score for seizure grade, shortened the duration o f seizures, as well as reduced the number of animals experiencing seiz ures during three of the four testing periods. MK801 reduced both the maximum seizure grade, and the number of animals experiencing seizures during sessions two and three. However, the dose of MK801 caused beha vioral side effects. Valproate actively decreased seizure grade, while it modestly acted to attenuate seizure duration, extended the time to seizure onset, and reduced the number of animals experiencing seizure s on testing day 1. Remacemide hydrochloride and phenobarbital were no t effective. The method appears useful for evaluating the potential of agents to prevent acute febrile seizures. (C) 1998 Elsevier Science B .V. All rights reserved.