Stimulation of brain-stem protein synthesis by morphine

Rats were intoxicated with morphine as intraperitoneal (i.p.) single doses, or for 4 days (final dose 130 mg/kg b.w.) or for 13 days (final dose 340 mg/kg b.w.) using an ingestion method where intoxicated and control rats received the same amount of calories and fluid. The intoxicated groups showed different degrees of physical dependence, demonstrated by variously expressed abstinence symptoms after withdrawal of the drug or after administration of the opiate receptor antagonist naloxone. Soluble protein synthesis was measured in vivo in brain stem by double labelling with 3H and 14C valine and followed over time in the various rat groups after i.p. morphine injection in different doses. Protein synthesis in astroglial-enriched primary cultures from brain stem and secretion of labelled protein to the serum free incubation medium was also evaluated after morphine treatment. There were dose- and time-dependent effects of morphine on brain stem protein synthesis with an initial decrease and a later increase, 1-3 hr after a single dose of morphine administration. Following a morphine single dose of 25 mg/kg b.w. the stimulation was more rapid in onset and more pronounced in rats with a higher degree of physical dependence. Specific protein fractions including one with a subunit M.W. of approx. 80,000 were identified by electrophoretic separation of labelled proteins. Some similar protein fractions increased in synthesis and were released to the serum-free incubation medium when separating astroglial primary culture proteins after morphine treatment. It might be that the biphasic changes in protein synthesis after morphine administration underlie adaptive phenomena such as tolerance/physical dependence development and that some of the identified proteins including proteins synthesized in astroglial cells and secreted to the incubation media participate in these processes.