The influence of CGP-40116 on bicuculline evoked seizures in mice exposed to transient episode of brain oligemia

To assess the role of NMDA receptors in the modulation of a brain tolerance after a transient cerebral mild ischemia, adult mice were exposed for 30 m in to bilateral clamping of the common carotid arteries (BCCA) under pentob arbital anaesthesia. The competitive NMDA antagonist CGP-40116 was administ ered intraperitoneally (IP) in two experimental paradigms: a) acute treatme nt: twice, 4.0 mg/kg; 1,5 hour before the clamping of vessels and 6 hours a fter re-circulation and b) chronic treatment in a dose of 1.0 mg/kg; starte d 24 hours after re-circulation and continued once daily for 13 days with t he last injection 24 hours before the induction of convulsions. Seizures we re evoked with bicuculline (3.5 mg/kg, IF) 14 days after BCCA. Transient br ain oligemia induced protection against bicuculline toxicity. The acute tre atment with CGP-40116 only partially diminished the anticonvulsant phenomen on. In contrast, the chronic treatment with the drug markedly potentiated t he effect. It can be concluded that NMDA receptors only partially participa te in the induction of a protective effect against bicuculline toxicity aft er BCCA. The chronic treatment with low doses of the NMDA antagonist may en hance the brain tolerance, possibly due to the chemical preconditioning.