Potentiating action of midazolam on GABA-mediated responses and its antagonism by Ro 14-7437 in the frog spinal cord

The effect of midazolam, a new water-soluble benzodiazepine, on an in vitro slice preparation of the frog spinal cord was investigated using electrophysiological recordings. Midazolam potently (ED50 = 1 nM) enhanced the depolarizing action of GABA on primary afferent fibres while leaving the depolarizing effect of glutamate, glycine or high K+ solutions unchanged. Concentrations of midazolam higher than 100 nM had an antagonistic effect on GABA responses. Ro 14-7437 was a powerful and selective antagonist of the midazolam potentiation without affecting control responses to GABA, glutamate or high K+. The antagonism of GABA responses induced by high doses of midazolam was not sensitive to Ro 14-7437. Our data suggest that midazolam is a very potent and selective modulator of GABA responses: this finding illustrates that electrophysiological techniques can detect specific effects of very low concentrations of benzodiazepines on a CNS slice preparation with well preserved architectural organization.