Respiratory mu-opioid and benzodiazepine interactions in the unrestrained rat.

Interactions of mu-opioid receptors with the benzodiazepine system were studied by examining the modulatory effects of flumazenil (a benzodiazepine antagonist) and alprazolam (a benzodiazepine agonist) on the respiratory effects of the opioid peptide dermorphin. Dermorphin, 1-30 nmol administered i.c.v., to conscious, unrestrained rats decreased ventilation rate (VR) and minute volume (MV) dose-dependently. The ventilatory depression was antagonized by naloxone and by the benzodiazepine antagonist flumazenil. The benzodiazepine alprazolam potentiated the respiratory inhibition of a small (1 nmol) dose of dermorphin but antagonized that of a higher dose (3 nmol). The results suggest that the benzodiazepine/GABA receptor complex modulates respiratory depression induced by central mu-receptor stimulation in the rat.