Effect of midazolam with and without flumazenil on conditioned hypoalgesia

The hot plate paradigm for pain threshold was used in two experiments to investigate the effects of the benzodiazepine midazolam and the benzodiazepine antagonist flumazenil on the acquisition of conditioned hypoalgesia. In Experiment 1, an infusion of midazolam (10 micrograms) into the nucleus accumbens, but not into the striatum or intermediate reticular zone, resulted in a complete blocking of the acquisition of conditioned hypoalgesia. Two possible mechanisms underlying this disruption in learning are discussed. Experiment 2 revealed that systemically administered flumazenil (10 mg/kg) was capable of blocking the effect of midazolam observed in Experiment 1 only when administered in such a manner as to prevent any activity of midazolam at benzodiazepine receptors. These results suggest that the effect of midazolam observed in Experiment 1 was mediated by a relatively short action at benzodiazepine receptors.