KYNURENIC ACID AND QUINOLINIC ACID ACT AT N-METHYL-D-ASPARTATE RECEPTORS IN THE RAT HIPPOCAMPUS

Abstract

Responses evoked by several amino acid excitants, including the tryptophan metabolite quinolinic acid, were recorded intracellularly from CA1 pyramidal neurons on rat hippocampal slices. Quinolinate, N-methyl-D-aspartate (NMDA), ibotenate and (.+-.)-cis-1-amino-1,3-dicarboxycyclopentane produced excitations characterized by burst firing of action potentials, tetrodotoxin-resistant spiking and apparent increases in input resistance measured with brief hyperpolarizing current pulses. L-Glutamate, kainate, quisqualate and (.+-.)-2''-amino-3-hydroxy-5-methyl-4-isoxazole-3''-propionate depolarized CA1 pyramidal neurons and induced apparent decreases in input resistance. Quinolinate-NMDA-, and ibotenate-induced focal depolarizations, but not L-glutamate, kainate- or quisqualate-induced reponses, were strongy antagonized by specific NMDA receptor antagonists. The tryptophan metabolites kynurenic acid, at concentrations that antagonized focal depolarizations produced by NMDA, ibotenate and the endogenous excitant quinolinate, did not antagonize quisqualate or L-glutamase responses. In addition to its NMDA-type antagonist action, hyurenate blocked kainate-induced focal depolarizations.