The effects of benzodiazepine agonists, inverse agonists and Ro 15–1788 on the responses of the superior cervical ganglion to GABA in vitro

Abstract

The effects of benzodiazepines and their antagonists on the responses to γ‐aminobutyric acid (GABA) of the superior cervical ganglion of the rat were examined using extracellular recording. Chlordiazepoxide (1 μm to 28.9 μm) and flurazepam (145–725 nm) increased the responses of the ganglion to GABA and the increases were antagonized by Ro 15–1788, at 3.34 μm. The concentration of GABA used was 9.7 μm which gave half‐maximal responses. Chlordiazepoxide similarly increased the responses of the ganglion to GABA 38.8 μm in the presence of bicuculline 27.2 μm. This concentration of GABA gave, with bicuculline, responses of a similar magnitude as those to 9.7 μm in the absence of bicuculline. Bicuculline did not affect the actions of chlordiazepoxide or the antagonism by Ro 15–1788. Ro 15–1788 did not affect the increases in GABA response caused by pentobarbitone or by phenobarbitone in the presence of bicuculline. Ethyl β‐carboline‐3‐carboxylate (βCCE) (207 nm to 1 μm) significantly decreased the responses to GABA in the presence and in the absence of bicuculline. The decreases were antagonized by Ro 15–1788 (3.34 μm). βCCE at 2.1 μm and above did not significantly change the responses to GABA. Methyl β‐carboline‐3‐carboxylate (βCCM) at 88 to 440 nm significantly decreased the responses to GABA. The decreases were antagonized by Ro 15–1788 (3.34 μm) and were also seen in the presence of bicuculline. High concentrations of Ro 15–1788 decreased the responses to GABA, 9.7 μm, but increased the responses to GABA 38.8 μm in the presence of 27.2 μm bicuculline. The pattern of effects of the benzodiazepines, β‐carbo lines and low doses of Ro 15–1788 on the responses to GABA was similar to the effects of these compounds on seizure threshold and anxiety‐related behaviour in vivo. 1984 British Pharmacological Society