The possible modulation of morphine analgesia by the supramolecular GABA receptor complex

In the present study, the mechanism of the antagonistic action of 0.5 mg/kg diazepam on the analgesic effect of morphine was investigated. While Ro 15-1788, a benzodiazepine receptor antagonist, was found to partially reverse the inhibitory action of diazepam on morphine analgesia, a chloride channel blocking agent, picrotoxin, produced complete antagonism of the action of diazepam. Furthermore, picrotoxin potentiated the partial antagonistic effect of Ro 15-1788 at a normally ineffective dose to affect the 0.5 mg/kg diazepam-morphine dose-response curve. These overall effects of picrotoxin on the supramolecular GABA receptor complex are discussed.