SELECTIVE ANTAGONISM BY BENZODIAZEPINES OF NEURONAL RESPONSES TO EXCITATORY AMINO ACIDS IN THE CEREBRAL CORTEX

Abstract

1 The recently discovered benzodiazepine receptor exists in high concentration in the cerebral cortex. We have, therefore, examined the effects of diazepam and chlordiazepoxide on cortical neurone responses to excitatory and inhibitory amino acids and acetylcholine, in the cortex of rats anaesthetized with urethane. 2 Chlordiazepoxide applied by microiontophoresis reduced the responses to glutamate and aspartate but acetylcholine responses were unaffected on most cells even by much higher doses of benzodiazepine. γ-Aminobutyric acid (GABA) and taurine responses were unaffected on most cells, but were reduced on 4 of 25 units. After intravenous diazepam, responses to GABA and taurine were reduced on 3 cells and unchanged on 11. 3 On Purkinje cells in the cerebellum a number of cells (5 of 16) exhibited a substantial increase in responses to GABA and taurine following intravenous or iontophoretic application of benzodiazepines. 4 It is suggested that the highly selective reduction of excitatory amino acid responses in the cerebral cortex may be of particular relevance to the behavioural effects of benzodiazepines.