[Relationship between morphine-induced respiratory depression and the cholinergic system of respiratory center]

Morphine (0.5-4 mg/kg, iv) caused dose-dependent decreases of respiratory frequency (FR), minute volume (Vm) and PaO2 and an increase of PaCO2 in rabbits. These effects of morphine were reversed by pilocarpine (2.5 mg/kg, icv) .4-Amino pyridine (4-AP, 1.5 micrograms/kg, icv) caused increase of FR and PaO2 and reduction of PaCO2 with marked increase in Vm. When 4-AP was administered in combination with different doses of morphine, the respiratory depressant effect was reduced and the dose-effect curve was shifted to the right. Following administration of reserpine (1 mg/kg, iv) which depleted the brain of its catecholamine content, morphine (4 mg/kg, iv) was still capable of decreasing FR and Vm, and 4-AP could abolish this effect completely. Morphine (4 mg/kg) caused the most dramatic reduction of Ach contents in pons and medulla oblongata in rabbits 30 min after administration, and remained so until 60 min. Varying the dose of morphine (2-8 mg/kg) caused dose-dependent reduction of Ach contents in the above mentioned brain areas. The time course and dose-effect of respiratory depression showed a close correlation with those of the decline of Ach contents in lower brain stem (r = 0.9301, P less than 0.01). The results showed that the respiratory depression by morphine was related to the reduction of Ach contents in lower brain stem and hence causing decrease of Ach release.