Influence of caffeine and midazolam on gamma-aminobutyric acid-evoked responses in the frog spinal cord.

The recently reported potentiation of gamma-aminobutyric acid (GABA) evoked depolarizations by caffeine in the frog spinal cord might involve an interaction with GABA-linked benzodiazepine receptors. This possibility was investigated using a new potent benzodiazepine, midazolam, and a benzodiazepine antagonist, Ro 147437. Caffeine or midazolam enhanced the amplitude of submaximal GABA responses by about 50%; when equieffective enhancing doses of these compounds were simultaneously applied, GABA depolarizations were usually depressed below control levels. It was however possible to detect a narrow range of concentrations of midazolam which had an additive effect to the enhancement by caffeine. Ro 147437 did not block caffeine-induced potentiations of GABA responses. It is suggested that caffeine and benzodiazepines have distinct modes of action in modulating GABA-induced depolarizations in the in vitro spinal cord of the frog.