Effects of morphine on DNA synthesis in neonatal rat brain.

Several observations have led to the hypothesis that endogenous opioids may modulate the growth and development of the brain. In the present study, we have examined the effect of morphine on the incorporation of [3H]thymidine into the DNA of neonatal rat brains in vivo and in vitro. We have found that morphine, when administered to one-day-old rats, inhibited [3H]thymidine incorporation into brain DNA in a long-lasting, naloxone-reversible manner. Morphine inhibited DNA synthesis in animals one and 4 days of age but not in older animals. This effect was tissue-specific, and did not appear to be due simply to respiratory depression or decreased availability of precursor to the brain. Naloxone, when administered acutely, or naltrexone, chronically, had no effect on [3H]thymidine incorporation, indicating that endogenous opioids do not tonically depress DNA synthesis. When neonatal brain tissue was incubated with morphine in vitro. [3H]thymidine incorporation values were not different from controls. These data indicate that the effect of morphine on DNA synthesis in vivo may be an indirect one, rather than a direct action on proliferating cells.