Ro 15-1788 is a potent antagonist of benzodiazepines in the olfactory cortex slice

The olfactory cortex slice from the guinea pig has been used to test the benzodiazepine antagonist, Ro 15-1788. Bath application of muscimol has a GABA-mimetic effect on the resting input conductance of these neurones. Benzodiazepines increase the potency of muscimol and increase the duration of postsynaptic inhibitory conductance. To measure the effect of muscimol, the input conductance was measured either directly using intracellular microelectrodes or by measuring its effect on the amplitude of the evoked compound potentials recorded from the slice surface after stimulating the lateral olfactory tract. The potentiation of postsynaptic inhibition produced by benzodiazepines was measured indirectly by their effect on the amplitude of the second of two evoked compound potentials. All of the potentiating effects of diazepam, clonazepam, flurazepam and chlordiazepoxide were blocked by Ro 15-1788 (0.01-10 mumol/l). Ro 15-1788 up to a concentration of 10 mumol/l had no effect on any of the synaptic or electrical responses when applied alone. General anaesthetics which also potentiate inhibition were unaffected by Ro 15-1788. It is concluded that Ro 15-1788 is a highly potent and specific benzodiazepine antagonist in this preparation.