The influence of MK-801 on bicuculline evoked seizures in adult mice exposed to transient episode of brain ischemia

The aim of the study was to examine the role of NMDA receptors in modulatio n of protective effect against bicuculline toxicity after transient brain i schemia in mice. Animals were exposed for 30 min to bilateral clamping of t he common carotid arteries (BCCA) in anaesthesia. MK-801 was administered i ntraperitoneally in two paradigms: a) acute treatment: twice, 1.0mg/kg; 1 h our before clamping and 6 hours after re-circulation and b) chronic treatme nt: 0.1 mg/kg; started 24 hours after re-circulation and continued once dai ly for 13 days, the last injection was administered 24 hours before seizure induction. 14 days after BCCA, the animals were injected with bicuculline (3.5mg/kg s.c). A significant decrease in seizure susceptibility could be o bserved in BCCA treated mice compared with sham-operated controls. Acute tr eatment with MK-801 did not affect seizure activity both in sham and BCCA m ice. Chronic treatment with the drug potentiated anticonvulsant effect of b rain ischemia but had no influence on seizure activity in sham-operated mic e. The analysis of GABA content in brain tissue performed 14 days after BCC A showed a moderate increase in vehicle-treated mice and significant elevat ion after chronic treatment with MK-801. It can be suggested that NMDA rece ptors are not involved in the induction of a protective effect against bicu culline toxicity after transient brain ischemia. The prolonged treatment wi th low doses of MK-801 may potentiate a developed process in a mechanism of chemical preconditioning.