Electrophysiological And Pharmacological Studies On Kainic Acid-Induced Neuronal Activation

Abstract

The excitotoxic hypothesis proposes that amino acids exert their neurotoxic action via an excessive neuronal excitation. In concordance with the extreme sensitivity of CA₃ pyramidal hippocampal neurons to the neurotoxic action of kaïnic acid (KA), these neurons were found to be exquisitely sensitive to the excitatory action of KA applied microiontophoretically. The excitatory action of KA on CA₁ but not on CA₃ neurons was selectively antagonized by low intravenous doses or low current microiontophoretic applications of benzodiazepines (BZD). This effect of BZD was not mimic by phenobarbital or chlorpromazine and was blocked by the specific BZD antogonist, RO 15-1788. The blockade of KA-induced activation of CA₁ pyramidal neurons is not due to an enhanced GABAergic activity since BZD, given at the same dose, failed to potentiate the effect of GABA; furthermore, direct microiontophoretic applications of GABA did not have any selective effect on KA-induced activation. It is proposed that the antagonism of an endogenous ligand for these “KA-sensitive” receptors might be related to their clinical anxiolytic effect.