Abstract
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 (δ antagonist), β-funaltrexamine (μ antagonist), and Mr2266 (κ antagonist)—were tested. The morphine-induced depression in the resting respiration was antagonized by pretreatment with the κ antagonist, not with the μ or δ antagonist. Furthermore, the morphine-induced attenuation in the magnitude of the poststimulus suppression was also blocked by the κ antagonist, but not by the μ or δ 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 κ opioid receptors. The possibility that the κ3 receptor, one of the κ receptors subtypes, mediates the two kinds of morphine effects has been discussed.
