Effect of chronic morphine on plasma and brain beta endorphin and methionine enkephalin in pregnant rats and in their fetuses or newborn.

Normal or pregnant rats were treated orally for 21 days or throughout pregnancy with water or increasing doses of morphine and killed on days 7, 14, and 21 of pregnancy and 1 day post partum. At these time intervals, plasma, pituitary, and hypothalamic concentrations of beta-endorphin and methionine enkephalin were measured in normal and pregnant rats. Moreover, pituitary and hypothalamic concentrations of the two peptides were also measured in fetuses and newborn. Plasma beta-endorphin and methionine enkephalin increased significantly during pregnancy without any specific effect of morphine. Pituitary concentrations of beta-endorphin were not modified either by pregnancy or morphine treatment, while methionine enkephalin concentrations increased on days 7 and 11 of pregnancy, in both water- and morphine-treated rats. The pattern of the two peptides in the hypothalamus is completely superimposable to the one present in the pituitary with the exception of an increase of beta-endorphin on day 21 of pregnancy, which is more evident in control animals. Consistently with our observations in human newborn and the neurological dysfunctions we observed in them, the concentrations of both the peptides are significantly increased in the hypothalamus of fetuses and newborn of morphine-treated mothers, while in the pituitary only beta-endorphin concentrations are increased.