An efficient method for time course studies of antiepileptic drugs using the kindled rat seizure model

A new method of testing the time course of anticonvulsant drugs in the kindled rat seizure model was investigated. To determine whether there are inhibitory effects of a kindled seizure on subsequent seizures, groups of 10 rats were made to convulse three times consecutively with interstimulation intervals of 0.5, 1, and 1.5 hr. Only with an interstimulus interval of 0.5 hr was there evidence of potential inhibitory effects lasting long enough to affect subsequent seizures. The time course of the anticonvulsant activity of diazepam was determined using two protocols: one in which groups of kindled rats were stimulated once and a second protocol in which animals were stimulated two times (at least 1.5 hr apart) following diazepam administration. The time courses of diazepam's inhibitory effect on kindled seizures obtained with each protocol were not significantly different. The data indicate that multiple stimulation episodes can be utilized in kindled rats to determine the time course following single administration of antiepileptic drugs.