Abstract
Since the inhibition of cortical neurons evoked by electrical stimulation of the surface of the cerebral cortex is believed to be mediated by endogenous GABA, the effects of five benzodiazepines on this inhibition were studied in cats anesthetized with fluothane or methoxyflurane. The benzodiazepines used were Ro 217ndash;3981, flurazepam, chlordiazepoxide, medazepam and clozapine, because their water solubility allows their microiontophoresis. The degree of inhibition of single cortical neurons induced to fire submaximally by Na L-glutamate was measured from peristimulus histograms generated by the extracellularly recorded spikes. Both the percentage of GABA potentiation by equal iontophoretic doses of the five benzodiazepines, as well as the iontophoretic doses of the benzodiazepines necessary to induce the same degree of GABA-potentiation, agreed well with the relative affinities of these drugs for the benzodiazepine receptor in rat brain membranes in vitro as reported by Braestrup and Squires [2], which are known to correlate well with several pharmacological tests predictive of anxiolytic activity in man.
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