Antagonism between bicuculline and GABA in the cat brain

Abstract

(1) An investigation was made of the effects of bicuculline on the inhibition by amino acids of neurones in the lateral vestibular nucleus, the ventrobasal thalamus, and the cerebellar, hippocampal and cerebral cortices of cats anaesthetized with pentobarbitone sodium. (2) In all regions, bicuculline reversibly antagonized the action of GABA without modifying that of glycine. In contrast strychnine suppressed the inhibitory effect of glycine but not that of GABA. (3) The inhibition by β-alanine of the firing of thalamic, cerebellar, hippocampal and cerebral cortical neurones was reduced by both bicuculline and strychnine; the inhibition of lateral vestibular neurones by β-alanine, like that of spinal neurones, was insensitive to bicuculline. (4) The classification of depressant amino acids on the basis of antagonism by bicuculline and strychnine is different when these substances are tested on spinal and supraspinal neurones. (5) Concentrations of bicuculline adequate to modify the sensitivity of Purkinje cells to GABA had little or no effect on the inhibition of these neurones by noradrenaline. (6) The relatively high degree of specificity of bicuculline as a GABA antagonist indicates that this alkaloid is of considerable value in determining whether or not a particular inhibitory pathway could operate by releasing GABA as an inhibitory transmitter.