Abstracts

Rationale: Seizures induced by systemic administration of NMDA in immature rats were recently suggested as a model of infantile spasms. Present study was designed to analyze age- and drug-related differences in pharmacological sensitivity of NMDA-induced seizures in two age groups of developing rats. Methods: Seizures were induced in P12 and P25 Wistar rats by intraperitoneal injection of NMDA (60 and 300 mg/kg, respectively). Vigabatrin (VGB; 300-1200 mg/kg) and valproate (VPA; 100-400 mg/kg) were administered 24 h or 15 min before NMDA. After NMDA administration, animals were observed for 30 min and incidence of flexion, clonic (i.e. Racine stage 3), and generalized tonic-clonic (GTCS) seizures as well as seizure latency were recorded. Mortality was registered till the end of observation period. Results: In P12, NMDA induced flexion seizures in 93% and GTCS occurred in 89% of animals. Clonic seizures were never observed. Mortality was 93%. VGB in doses 600 and 1200 mg/kg decreased incidence of flexion seizures by 37 and 51% respectively. Other parameters were not affected. VPA in doses 100 and 200 mg/kg decreased incidence of GTCS to 56 and 67%. In P25, NMDA induced GTCS in 100% of controls. Flexion seizures were never observed. Clonic seizures develop only in 18% of rats. VGB had no effects on any measured seizure parameter. Administration of VPA in doses 300 and 400 mg/kg increased incidence of clonic seizures to 75%, but other seizure parameters remain unchanged. Conclusions: Our results demonstrate age-specific effects of VGB and VPA in a model of NMDA-induced seizures. Supported by a Research Project LC554.