MORPHINE AND THE INCORPORATION OF p₁³² INTO BRAIN PHOSPHOLIPIDS OF NONTOLERANT, TOLERANT AND ABSTINENT GUINEA PIGS

¹ National Institute of Mental Health, Addiction Research Center, Lexington, Kentucky

This investigation was initiated to determine the effect of administered morphine on the incorporation of P₁³² into cerebral cortex phospholipids from nontolerant, tolerant and abstinent guinea pigs. After a single 40-mg/kg (free base) s.c. injection of morphine, guinea pigs were sacrificed 1, 4 and 10 hr later. Cerebral cortex slices from these guinea pigs were incubated without and with the additions of 10^-2 to 10^-6 M morphine. A significant stimulation (42-115%) of the incorporation of P₁³² into the phospholipids was observed with cortical slices incubated without additional morphine from animals sacrificed at 1 hr. P₁³² uptake into phosphatidylinositol, phosphatidylcholine, phosphatidylserine and phosphatidylethanolamine was significantly stimulated (45 to 112%) in cortical slices incubated without additional morphine from animals sacrificed at 4 hr. Essentially no effect on the phosphatides was obtained with in vivo levels of morphine from guinea pigs sacrificed 10 hr after drug. Absence of an effect on phospholipid metabolism was observed with cortical slices incubated without additional morphine from chronically morphine-treated animals. The effect of additional morphine (10^-3-10^-6 M) on the phosphatides of slices from these animals appeared to be less than that found with nontolerant animals. No phospholipid effect occurred with cortical slices from abstinent guinea pigs (24 hr-3 months). However, the addition of 10^-2 M morphine to these slices dramatically stimulated the uptake of P₁³² into phosphatidic acid (303%) and triphosphoinositide (370%). Morphine-C¹⁴ levels of 121 nmol/g of brain were obtained 1 hr later for the tolerant guinea pigs and from 1.10 to 0.10 nmol/g 1 to 10 hr after drug in the nontolerant animals. It is concluded that subcutaneously administered morphine stimulates phospholipid metabolism in cortical slices from nontolerant guinea pigs, an adaptation to this effect occurs in the chronically morphine-treated animals and P₁³² uptake into polyphosphoinositides from abstinent guinea pigs is markedly enhanced in the presence of added morphine.