Abstracts

RATIONALE: Pre-clininal antiepileptic efficacy of new antiepileptic drugs (AEDs) is typically assessed by using experimental models, in which seizures are evoked electrically or chemically. There is, however, a general agreement that in an ideal model of human temporal lobe epilepsy (TLE), seizures should be spontaneous, and their electrographic and behavioral characteristics should resemble that in human TLE. Here, we tested the effect of antiepileptic drugs on spontaneous seizures in a recently developed model of TLE, in which status epilepticus (SE) is followed by a latency period, and spontaneous seizures. METHODS: SE was induced in adult Spraque-Dawley rats by electrically stimulating the amygdala. Three months after SE, animals were followed for a week by a continuous video-EEG monitoring in order to detect spontaneous seizures, and to establish baseline seizure frequency and duration. Thereafter, carbamazepine (CBZ, 120 mg/kg/d), valproic acid (VPA, 600 mg/kg/d), ethosuximide (ETX, 400 mg/kg/d), lamotrigine (LTG, 20 mg/kg/d), or vigabatrin (VGB, 250 mg/kg/d) were administered for 5-11 days. Antiepileptic effect was monitored by a continuous video-EEG recording. RESULTS: In all animals, LTG and VPA reduced the mean seizure frequency by 84% (p<0.05) and 77% (p<0.05), respectively. Over 50% reduction in seizure frequency was found in 100% of LTG, 100% of VPA, 40% of CBZ, and 50% of ETX, and 33% of VGB treated rats. A significant decrease in seizure duration was found in VPA (from 41 to 20 sec, p<0.05) and ETX treated rats (from 57 to 41 sec, p<0.05). CONCLUSIONS: In chronically epileptic rats, spontaneous seizures of temporal lobe origin are controlled by the same AEDs that are antiepileptic in patients with TLE. This model offers a new tool to predict the clinical efficacy of new compouns in chronic study designs that resemble study protocols used in clinical trials in humans. (Supported by Academy of Finland, Sigrid Juselius Foundation and Vaajasalo Foundation).