4. Suppression of hippocampal kindling seizures by lorazepam and levetiracetam

Introduction Benzodiazepine GABA enhancers and levetiracetam are known to be effective in suppression of kindling seizures, but the effects of these antiepileptic drugs on regional after discharges adjacent to the kindling sits are largely unknown. We explored this issue in a mouse model of hippocampal kindling and compared the effects of lorazepam and levetiracetam on hippocampal and piriform after discharges as the piriform cortex is thought to play a critical role in genesis of kindling seizures. Methods C57 black mice received electrode implantations in unilateral hippocampal CA3 and piriform cortical areas and then underwent twice daily hippocampal stimulation for a few weeks. The effects of antiepileptic drugs were tested in fully kindled mice. Lorazepam (1.5 mg/kg) or levetiracetam (100 mg/kg) was applied by an intra-peritoneal injection 15 or 60 min before hippocampal stimulation. The effects observed following similar saline injections were taken as baseline controls. Results Evoked motor seizures and associated piriform after discharges were abolished by lorazepam whereas the durations of corresponding hippocampal afterdischarges were unchanged from baseline controls (n = 6 mice). Evoked motor seizures and corresponding hippocampal and piriform afterdischarges were significantly decreased by levetiracetam, but shortened afterdischarges were more pronounced in the piriform than in the hippocampal area (n = 6 mice). Summary Lorazepam may suppress motor seizures by inhibiting seizure spread from the stimulated hippocampal focus to the piriform cortex and other brain areas, and levetiracetam may inhibit both focal/hippocampal seizures and seizure spread in our model.