Effects of anticonvulsants on hyperthermia-induced seizures in the rat pup

We studied the effects of phenobarbital (PB), valproic acid (VPA), and phenytoin (PHT) on the electroencephalograms and behaviorally defined seizure threshold temperatures in rat pups exposed to ambient hyperthermia on the fifth day of life. Animals injected with 10, 20, or 40 micrograms PB/g body weight (GBW) or 80, 150, or 300 micrograms VPA/GBW daily from the second day of life showed seizure temperature thresholds that were about 1.0 degree C higher than those of controls. Pups injected with PHT had thresholds that were equal to or lower than those in controls despite blood levels greater than 20 micrograms/ml. Preictal rhythmic sharp wave activity appeared in VPA-injected animals at temperatures below the threshold temperature. All experimental animals showed electrographic epileptiform activity at the threshold temperatures. We conclude that this animal model shows similar anticonvulsant efficacies to those found in human febrile seizures. This model may be useful in determining the efficacy of potentially useful anticonvulsant drugs and their mechanisms of action.