Morphine inhibits resting respiration, but it attenuates reflexive respiratory suppression in anesthetized cat...

Noxious stimulation of thin-fiber muscular afferents induces a reflexive respiratory suppression that we call "poststimulus respiratory suppression." In anesthetized, vagotomized, paralyzed, and artificially ventilated cats, morphine depressed the level of resting respiration (inhibitory effect on resting respiration) and attenuated the magnitude of the poststimulus respiratory suppression (excitatory effect on the reflexively modified respiration). These two kinds of morphine effects were antagonized by naloxone, suggesting the participation of opioid receptors. To clarify the opioid receptor subtypes responsible for these effects of morphine, three type-selective opioid antagonists-naltrindole (delta antagonist), gamma-funaltrexamine (mu antagonist), and Mr2266 (kappa antagonist)-were tested. The morphine-induced depression in the resting respiration was antagonized by pretreatment with the kappa antagonist, not with the mu or delta antagonist. Furthermore, the morphine-induced attenuation in the magnitude of the poststimulus suppression was also blocked by the kappa antagonist, but not by the mu or delta antagonist. In conclusion, (1) morphine inhibits resting respiration, but it attenuates the magnitude of the poststimulus respiratory suppression; (2) both these morphine effects are mediated by kappa opioid receptors. The possibility that the kappa(3) receptor, one of the kappa receptors subtypes, mediates the two kinds of morphine effects has been discussed.