Distribution of 14C-morphine and macromolecules in the brain and liver and their nuclei in pregnant rats and their foetuses after infusion of morphine into pregnant rats at near-term.

Abstract

Abstract: Timed‐pregnant (day 21 or 22) Sprague‐Dawley rats were administered 14C‐morphine (2.85 mci/mmol) 5 mg/kg/hr, or saline in equivalent volumes, by continuous intravenous infusion for periods of up to 4 hrs. The brains and livers of the maternal rats and of their foetuses were collected and their nuclei were isolated. The tissues and nuclei isolated from them were analyzed for DNA, RNA, protein content and radioactivity. Morphine infused maternal rats exhibited no significant difference in the total amounts of DNA, RNA and protein in the brain or in the concentration of these constituents in brain nuclei. Foetuses of morphine infused mothers exhibited no significant difference in the total amounts of macromolecules in the brain or in the concentration of DNA and protein in brain nuclei. It was found, however, that the concentration of nuclear RNA in foetal brain of morphine infused mothers was significantly lower at 4 hrs than that of saline infused controls. It was concluded that RNA synthesis in foetal brain must be much more sensitive to the inhibitory effect of morphine on macromolecular synthesis than that in maternal brain. The change in nuclear RNA concentration in foetal brain became significantly different when morphine reached its highest level in foetal brain nuclei. The morphine concentration (pmol 14C‐morphine equivalents per mg DNA) in the brain of foetal and maternal rats was the same at each time period, whereas the maternal liver levels were at least eight times greater than those in foetal liver. The concentrations in foetal brain nuclei were 2–14 times greater than those in maternal brain nuclei, whereas levels in the latter were found to be low and virtually constant at all time periods tested. Similar differences were found between foetal and maternal liver nuclei when the results were expressed as a percentage of the concentration in respective liver tissue. It was concluded that foetal brain nuclei have a greater capacity to bind or retain morphine than maternal brain nuclei and the phenomenon of differential distribution of morphine within brain cells is, among other factors, related to differences in sensitivity to morphine analgesia and other effects of morphine in young and old rats. The results were interpreted in terms of an inhibitory effect of morphine on transcription in foetal brain resulting from intranuclear accumulation of morphine.