RELATIONSGIP 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 piloearpine (2.5 mg/ kg, icv). 4-Amino pyridine (4-AP, 1.5 μg / 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 (1mg/ kg, iv) which depleted the brain of its catecholamine content, morphine (4mg / 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 shewed a close correlation with those of the decline of Ach contents in lower brain stem (r=0.9301, P<0.01). The results, showed that the respiratory depression by morphine was relatedto the reduction of Ach contents in lower brain stem and hence causing decrease of Ach release.