THE MODE OF ACTION OF MORPHINE ON THE UPTAKE OF CARBACHOL AND DECAMETHONIUM BY SLICES OF RAT CEREBRAL CORTEX

¹ Department of Pharmacology and Brain Research institute, UCLA School of Medicine, Los Angeles, California

Slices of rat cerebral cortex in Krebs' fluid concentrate labeled carbachol and decamethonium (C₁₀) ; this uptake was inhibited by morphine. The concentration of morphine which halved the morphine-sensitive uptake of both carbachol and C₁₀ was approximately 15 µmol/liter. Thebaine was seven times more potent than morphine in blocking carbachol uptake, but the effects of thebaine on C₁₀ uptake were complex. Morphine reduced the uptake of carbachol by 85%, but only one-third of the uptake of decamethonium was morphine-sensitive. The effect of morphine on carbachol uptake is uninfluenced by the development of marked tolerance to morphine and the blocking action of morphine cannot be antagonized by nalorphine. The development of tolerance to morphine (100 mg/kg twice a day for 7 days) was accompanied by a reduced ability of brain slices to concentrate C₁₀. Attempts to study the interaction of morphine and nalorphine are complicated by the fact that nalorphine itself reduces C₁₀ uptake. When morphine and nalorphine act together no effect due to morphine can be detected, suggesting some form of antagonism.