The effects of three doses of SC-13504 were determined on prekindled and partially kindled hippocampal seizures in rats. A dose of phenobarbital previously shown to be anticonvulsant in rats was used for comparison. The drugs were tested for effectiveness twice during the 12 sessions, once during session 2 to determine the prekindling effectiveness and once during the last session to determine the effectiveness against kindled seizures. After 11 stimulations, the seizures showed a significant increase in afterdischarge duration, clinical seizure severity, and time to return to normal EEG and the stimulus threshold showed a nonsignificant decrease compared to the first stimulation. These results indicate that the development of progressively more severe hippocampal seizures (kindling) can occur with just 11 days of stimulation. When stimulated at the control day threshold, 3 and 300 mg/kg SC-13504 provided anticonvulsant protection against both prekindled and kindled seizures, whereas 30 mg/kg SC-13504 was less effective. Animals stimulated until seizures occurred on drug days showed a dose-dependent decrease in afterdischarge duration and an increase in voltage threshold with all three doses of SC-13504. Phenobarital provided no protection against prekindled seizures but was very effective against kindled seizures. These results may indicate that phenobarbital is a more effective anticonvulsant against developing or developed limbic system seizures than against prekindled seizures. This paradigm may provide a model for testing the effectiveness of anticonvulsants during the progressive development of epileptic seizures.
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