Excitatory and inhibitory effects of morphine on the intercostal-to-phrenic respiratory reflex

The purpose of this study was to determine the effect of intravenously administered morphine on the intercostal-to-phrenic reflex in spinal (C1) cats. The carotid and vertebral arteries were ligated. In addition a metal clamp was placed around the neck and tightened in order to occlude all blood flow to the brain. The animals were vagotomized, paralyzed and ventilated artificially. End-tidal PCO2 and body temperature were kept constant by means of servocontrollers. The intercostal-to-phrenic reflex was activated by rhythmic tapping of the lower thorax anteriorly with a metal bar. Three different doses of morphine were used. The smallest dose (1 mg/kg) caused a marked stimulation of phrenic activity that lasted for more than 5 min. A larger dose (10 mg/kg) had only a mild excitatory effect. A much larger dose (50 mg/kg), on the other hand, caused inhibition of evoked phrenic activity. Possible mechanisms involved in mediating the dose dependent effects of morphine on the intercostal-to-phrenic reflex are discussed.