Amino acid incorporation during morphine intoxication. I: Dose and time effects of morphine on protein synthesis in specific regions of the rat brain and in astroglia-enriched primary cultures.

Uptake and incorporation of 3H-valine into soluble protein were studied in normal and in physically dependent rat brain, or in astroglial primary cultures at various times after the administration of morphine at different doses. There was an increased protein synthesis in striatum and brain stem of previously untreated rats 2-3 hr after low-dose morphine administration (10 mg/kg bw IP). The changes were completely reversed by naloxone (5 mg/kg bw, IP) administered 10 min prior to the morphine. During the first hour after IP administration of 25 mg morphine/kg bw there was a decrease in striatum and brain stem protein synthesis, followed by an increase in brain stem protein synthesis between 2 and 3 hr later. These changes were blocked by naloxone. In all brain regions studied 40 mg morphine/1 kg bw, IP inhibited protein synthesis, an effect partially reversed by naloxone (5 mg/kg bw, IP). Similar dose- and time-dependent effects were obtained from primary astroglia-enriched cultures from cerebral hemispheres, suggesting that low or moderate doses of morphine affect brain cell protein synthesis. At least one phase of increased synthesis was seen, but within a few hours of a high morphine dose the protein synthesis was decreased. After long-term morphine intoxication (13 days; final dose 340 mg/kg bw/day po) incorporation of 3H-valine in vivo into TCA-precipitable soluble proteins during 60 min decreased in the hypothalamus and in the occipital and entorhinal cortex, and was unchanged in other brain regions examined. An IP injection of morphine (10 or 25 mg/kg bw/day) to such animals resulted in a pronounced and rapidly occurring increase in protein synthesis in many brain regions. This was further demonstrated with gel electrophoresis in brain stem and hypothalamus, where higher 3H-labeling was seen in many protein bands. The labeling of one band from brain stem having approx 80,000 MW was especially pronounced. Incorporation of 3H-valine into membrane-bound proteins of brain stem changed in a similar way to the soluble proteins, but was not as pronounced.