Abstracts

Antiepileptic drugs (AEDs) have traditionally been tested on acute seizures, but animal models of chronic epilepsy with spontaneous seizures may be more useful for developing new drugs to treat the pharmacoresistant population. Recent research suggests that these models can be used efficiently for studying the effects of AEDs on epileptic seizures. A study from our group (Grabenstatter et. al, 2005) used a repeated-measures cross-over protocol in rats with kainate-induced epilepsy, and showed that topiramate reduced seizure frequency in a dose-dependent manner. The purpose of the present experiment was to evaluate how the widely used AED carbamazepine depressed spontaneous seizures in rats with kainate-induced epilepsy. Kainic acid was administered in repeated, low doses (5 mg/kg) every hour until each male Sprague-Dawley rat experienced convulsive status epilepticus for [gt]3 h. Focal field-potential recordings in freely-behaving rats (n= 8) receiving 30 mg/kg carbamazepine or vehicle (20% (2-Hydroxypropyl)-[beta]-cyclodextrin) were used to assess the effects of AED on spontaneous seizures using a repeated-measures, cross-over protocol. Spontaneous seizure frequency was significantly suppressed by 78.44% (p[lt]0.0001) after administration of 30 mg/kg carbamazepine. The same dose did not affect seizure duration. Convulsive seizures were reduced by 70.27% (p[lt]0.0001). Nonconvulsive seizures were also reduced, but only by 47.31% (p=0.0947). Carbamazepine (30 mg/kg) preferentially reduced convulsive seizures in spontaneously seizing rats with kainate-induced epilepsy. These data demonstrate that use of animal models with spontaneous seizures can provide valuable information about AEDs when implemented with EEG and video-monitoring. Carbamazepine elicited similar effects on convulsive and nonconvulsive seizures in rats with kainate-induced epilepsy as is observed clinically in patients with refractory temporal lobe epilepsy (i.e., nonconvulsive seizures were ineffectively treated)[italic].[/italic] (Supported by Epilepsy Foundation of America.)