The NMDA receptor antagonist 2-amino-5-phosphonovalerate blocks stimulus train-induced epileptogenesis but not epileptiform bursting in the rat hippocampal slice.
The role of N-methyl-D-aspartate (NMDA) receptors in producing stimulus train-induced bursting (STIB) was examined in area CA3 of the rat hippocampus. Extracellular recordings were made from the CA3 pyramidal cell layer. Bursting was induced by trains of electrical stimuli delivered to the stratum radiatum of CA3, or by bath application of NMDA. The specific NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV) was then bath applied to test its ability to block STIB and NMDA activated bursting. A dose-response relation for NMDA activation indicated that bath application of 1 and 5 microM NMDA had little or no effect on the response to a paired stimulus pulse (triggered response) and did not induce spontaneous bursting. Ten micromolar NMDA induced strong triggered and spontaneous bursting during the application of NMDA in 72% of the slices. Fifty to one hundred micromolar NMDA caused the abolition of the excitatory postsynaptic potential (EPSP) and orthodromic population spike and the decrease or abolition of the antidromic population spike. In the normal medium wash following 10 microM NMDA, those slices that produced triggered and spontaneous bursting in 10 microM NMDA underwent an early phase of decreased excitability in which spontaneous bursting occurred in only 6% of the slices that were bursting in NMDA. Later in the wash spontaneous bursting began occurring in half of the slices that were bursting in NMDA, and the excitability of the triggered bursts increased slightly. The ability of the NMDA receptor antagonist APV to block NMDA-activated bursting was tested. Bath application of 100 or 200 microM APV alone caused little change in the normal triggered response. When 10 microM NMDA was added to the APV solution, there was little or no change in the triggered response, and no spontaneous bursting occurred. However, when 100 or 500 APV was added to the NMDA solution after NMDA burst activation had occurred, triggered bursting was reduced, but not blocked, although spontaneous bursting was blocked. In those slices that continued bursting after the washout of NMDA, bath application of 100 or 500 microM APV reduced, but did not block, triggered bursting. Spontaneous bursting continued in all slices. The ability of APV to block the induction of bursting by trains of electrical stimuli was then tested.(ABSTRACT TRUNCATED AT 400 WORDS)
D015763:2-Amino-5-phosphonovalerate; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D004827:Epilepsy / Q000209:etiology / Q000517:prevention & control; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D016202:N-Methylaspartate; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000502:physiology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D014633:Valine