Effect of carbamazepine on spontaneous recurrent seizures recorded from the dentate gyrus in rats with kainate‐induced epilepsy

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Summary

Objective

Animal models of chronic epilepsy with spontaneous recurrent seizures (SRSs) may be useful in the discovery and mechanistic analyses of antiseizure drugs (ASDs). Carbamazepine (CBZ), a widely used ASD with a well‐defined mechanism, was analyzed in this proof‐of‐principle study to determine how a traditional ASD affects the properties of SRSs.

Methods

The effects of CBZ on electrographic SRSs recorded from the dentate gyrus were studied in freely behaving rats using a repeated, low‐dose kainate model of acquired epilepsy with a repeated‐measures, crossover protocol.

Results

Almost all seizure durations were >20 seconds. Both seizure likelihood and duration appeared to be similar between 1 and 8 hours after individual CBZ injections. CBZ‐induced decreases in seizure frequency were not significant at 10 mg/kg; however, at 30 mg/kg, seizure frequency was significantly reduced for convulsive but not nonconvulsive seizures. At 100 mg/kg, CBZ strongly suppressed both convulsive and nonconvulsive seizures. Although CBZ had a dose‐dependent effect on seizure frequency, CBZ did not affect seizure duration at any dose. The preceding interictal interval did not affect seizure duration; however, at 30 mg/kg CBZ, nearly all seizures were nonconvulsive when the interictal interval was <30 minutes (ie, during clusters).

Significance

Increased doses of CBZ (10‐100 mg/kg) suppressed the frequency but not the duration of convulsive and nonconvulsive seizures in the repeated, low‐dose kainate model. The repeated‐measures, crossover protocol, which requires relatively few animals and compensates for progressive increases in seizure frequency during epileptogenesis after status epilepticus, allowed quantitative analyses of clinically relevant and translatable properties of SRSs.

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