The effect of chronic treatment with sodium channel blocker lacosamide on early development of absence seizures in genetic absence epilepsy rats

Abstract

Objective: Lacosamide (LCM) is a new generation antiepileptic drug that affects the slow inactivation of voltagegated sodium channels. We studied whether chronic LCM treatment prior to onset of absence seizures was able to prevent/reduce the development of absence seizures in GAERS rats, a well-validated animal model of absence epilepsy and epileptogenesis. Drug effects on the duration, mean duration, number and spectral characteristics of spike-wave discharges (SWDs) were measured both 1 and 2 months after treatment withdrawal and compared with the ethosuximide (ETX) that has anti-epileptogenic activity in GAERS. Furthermore, the acute effects of LCM on SWDs in adult GAERS were evaluated.Methods: GAERS rats were administered either with LCM (10 mg/kg/day or 30 mg/kg/day, i.p) or ETX (25 mg/ kg/day, i.p) or saline (%0.9 NaCl) until PN60 for 40 consecutive days starting from PN20. Animals were stereotaxically implanted with cortical screw electrodes under ketamine/xylazine anesthesia at PN53. Following recovery period, EEG were recorded at PN60 (last day of drug administration)- 61-62, PN90-91-92 and PN120-121-122 time periods for 3 consecutive days.Results: The chronic treatment with both LCM and ETX led to an ~50% reduction in the development of spontaneous absence seizures in GAERS at PN90 and PN120 after the treatment withdrawal at PN60. The spectral analysis of EEG data revealed significant slowing of the peak frequency of SWDs in LCM treated animals at PN62.Conclusion: These results confirm that chronic LCM treatment modifies the development of absence seizures in GAERS and suggest that LCM exerts beneficial effects on absence seizure epileptogenesis.