Abstracts

Rationale: Levetiracetam (LEV) is a novel antiepileptic drug (AED) that has shown broad-spectrum effects on both convulsive and absence-like seizures in various epileptic rat models. The groggy (GRY) rat is a genetic animal model, which spontaneously exhibits an ataxic phenotype and absence-like seizures characterized by appearance 7 to 8-Hz spike-and-wave discharges (SWDs) on cortical EEGs concomitant with sudden immobility and staring. We have previously reported that conventional AEDs such as ethosuximide and valproic acid but not phenytoin inhibit epileptic seizures in the GRY rat. Therefore, this animal is considered as an animal model for absence seizures (Brain Research 2007,1133:168-177). In this study, we examined antiepileptic effects of LEV on the absence-like seizures using GRY rats. Methods: We first tested the acute effect of LEV (80 and 160 mg/kg,i.p.) on male GRY rats (n=10) implanted with four epidural EEG electrodes. Absence-like seizures were determined by appearance of SWDs by cortical EEG recordings concomitantly with behavioral observations. EEG was recorded for 15 min prior to injection of the test drug, and then postdrug EEG recordings were performed two times 15 min and 45min after drug administration for 15 min, respectively. In the second test, we examined the long-term effects of LEV on the seizures in GRY rats (n=10). After the cortical EEG recordings for 30 min as control period, LEV (80mg/kg,i.p.) or physiological saline (i.p.) were administrated. EEG recordings were performed four times (2, 6, 8 and 24 h) after the injection for 30 min. The frequency and duration of SWDs were measured and the total duration of each recording-period was calculated. The mean values of them were compared between pre- and post drug administrations to evaluate antiepileptic effects of LEV in the GRY rat using student’s t test.Results: LEV at doses of 80 and 160 mg/kg significantly (p < 0.01) reduced the total duration of SWDs in GRY rats 15-30 and 45-60 min after the drug administration although the dose-dependent effects were not evident (12% and 14% at the dose of 80mg/kg, 22% and 27% at the dose of 160 mg/kg compared with the value of control period, respectively). The number of SWDs was also significantly (p < 0.01) reduced 15-30 and 45-60 min after the drug administration (11% and 13% at the dose of 80 mg/kg, 35% and 28% at the dose of 160 mg/kg compared with the value of control period, respectively). In the second test, the SWDs were completely suppressed 2h after administration of LEV. This complete inhibition of the SWDs was still observed 6h after the LEV administration, while the significant inhibition was not seen 8-24h after the injection.Conclusions: Single LEV administration induced a suppression of the absence-like seizures in the GRY rat at least from 15 min to 6 h after the injection. This effect is likely to reach the maxim after 2-6 h post-treatment.