Low concentration of DL-2-amino-5-phosphonovalerate induces epileptiform activity in guinea pig hippocampal slices

Purpose: The specific mechanisms by which low concentrations of cyclosporin e induce seizures and low concentrations of phencyclidine provoke behaviora l excitation remain to be elucidated. Both compounds block N-methyl-D-aspar tate (NMDA) receptors. The aim of this study was to determine if low concen trations of the NMDA-receptor blockers increase the seizure susceptibility. Methods: Guinea pig hippocampal slices were exposed to artificial cerebrosp inal fluid containing the NMDA blocker DL-2-amino-5-phosphono-valerate (APV ; 0.1-10 muM). Extra-cellular field potentials were recorded front CA1 and CA3 regions. Results: Low concentrations of AIN induced epileptiform burst discharge,, ( 0.1-0.25 muM). whereas higher doses failed to decrease the seizure threshol d (1 -10 muM). Conclusions: The results indicate that the excitatory effect of low concent rations NMDA blockers may play a role in the neurotoxicity of aforementione d substances.