Pharmacology of the corticocaudate excitatory postsynaptic potential in the cat: evidence for its mediation by quisqualate- or kainate-receptors

Abstract

Caudate neurons were recorded with intracellular electrodes in halothane anaesthetized cats during microiontophoretic application of drugs and simultaneous stimulation of the corticocaudate pathway. Application of 2-amino-7-phosphonoheptanoic acid inhibited excitations induced by the N-methyl-D-aspartic acid receptor agonists N-methyl-D-aspartic acid and quinolinic acid, but not those elicited by quisqualic acid or activation of the cortico-caudate pathway. Selective inhibition of N-methyl-D-aspartic acid induced excitations was also found in vitro in the frog hemisected spinal cord preparation where a pA2-value of 5.5 against N-methyl-D-aspartic acid was determined. The endogenous tryptophan metabolite, kynurenic acid, antagonized excitations induced by N-methyl-D-aspartic, quisqualic, L-glutamic and kainic acid as well as the excitatory postsynaptic potential (EPSP) evoked in caudate cells by stimulation of the corticocaudate pathway, while action potentials elicited by an intracellularly applied depolarizing current were only slightly affected. In vitro experiments with the frog hemisected spinal cord preparation suggested that kynurenic acid might be a competitive antagonist of both N-methyl-D-aspartate and quisqualate receptors, with pA2-values of about 4.8 and 4.0, respectively. From these results it is concluded that the three-receptor concept for excitatory amino acids are proposed by Watkins and colleagues is probably applicable to the cat caudate nucleus and that the cortically evoked monosynaptic EPSP is mediated by a non-N-methyl-D-aspartate quisqualate- or kainate-receptor.