Abstracts

Rationale: Animal models with spontaneous seizures may serve as a valuable screen for antiepileptic drug (AED) development. New methods for rapid and effective testing of AEDs on animal models with spontaneous seizures are highly desired; the experimental protocols must control for inter-individual variation and seizure clustering observed in these models. This study evaluated the effect of carbamazepine (CBZ) administered in food pellets on spontaneous convulsive and non-convulsive seizures in rats with kainate-induced epilepsy. Methods: Repeated, low-dose kainate (5 mg/kg ip hourly) was administered to adult male rats (Sprague-Dawley; 150-250 g) until convulsive status epilepticus persisted for at least 3 h. CBZ (30, 100 or 300 mg/kg/day) was provided as food pellets in three 4-day cross-over trials (n= 8 rats) where animals received CBZ or control treatment, separated by 2 recovery days. The total amount of food provided corresponds to a normal caloric diet of 60 gm/kg/day. Results: CBZ significantly reduced mean seizure frequency in a dose-dependent manner. At 30 mg/kg/day, CBZ treatment consistently failed to block either convulsive or nonconvulsive seizures. However, at 100 and 300 mg/kg/d, CBZ nearly blocked all convulsive seizures, but these doses of CBZ had little or no effect on non-convulsive seizures. The effect of CBZ was consistent across the day-night cycle. Conclusions: This repeated-measures cross-over protocol offers a convenient approach for effective and rapid testing of potential AEDs. CBZ preferentially blocked convulsive seizures with little or no effect on non-convulsive seizures, even at the higher doses. Thus, the seizures that remained resistant to CBZ treatment were mostly non-convulsive. This study suggests that this animal model might be useful for testing drugs against pharmacoresistant epilepsy. (Supported by NIH)