Low concentration of DL-2-amino-5-phosphonovalerate induces epileptiform activity in guinea pig hippocampal slices.
OBJECTIVE
The specific mechanisms by which low concentrations of cyclosporine induce seizures and low concentrations of phencyclidine provoke behavioral excitation remain to be elucidated. Both compounds block N-methyl-d-aspartate (NMDA) receptors. The aim of this study was to determine if low concentrations of the NMDA-receptor blockers increase the seizure susceptibility.


METHODS
Guinea pig hippocampal slices were exposed to artificial cerebrospinal fluid containing the NMDA blocker dl-2-amino-5-phosphono-valerate (APV; 0.1-10 microM). Extracellular field potentials were recorded from CA1 and CA3 regions.


RESULTS
Low concentrations of APV induced epileptiform burst discharges (0.1-0.25 microM), whereas higher doses failed to decrease the seizure threshold (1-10 microM).


CONCLUSIONS
The results indicate that the excitatory effect of low concentrations NMDA blockers may play a role in the neurotoxicity of aforementioned substances.
Gorji
A
A
Institut für Physiologie, and Institut für Experimentelle Epilepsieforschung, Universität Münster, Münster, Germany. gorjial@uni-muenster.de
Speckmann
E J
EJ
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D000818:Animals; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects*; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D015763:2-Amino-5-phosphonovalerate