Long-term treatment of rats with morphine reduces the activity of messenger ribonucleic acid coding for the beta-endorphin/ACTH precursor in the intermediate pituitary.

Abstract

Chronic administration of morphine to rats for a period of 4 weeks resulted in a 50-60% decrease in the tissue concentrations of beta-endorphin and in the in vitro release from the neurointermediate pituitary. Incorporation of [3H]phenylalanine into isolated intermediate/posterior pituitaries in vitro revealed a reduction in the amount of label incorporated into the beta-endorphin/ACTH precursor to a similar extent (about 45%), but essentially no effect on the conversion of the precursor into beta-lipotropin and beta-endorphin. Extraction of mRNA from intermediate/posterior pituitaries followed by cell-free translation in a reticulocyte system showed no significant decrease in the total level of translatable mRNA. In contrast, the content of translatable mRNA coding for the beta-endorphin/ACTH precursor was significantly reduced by 50-60%. Thus, long-term treatment with morphine appears to depress beta-endorphin formation in the rat intermediate pituitary at the pretranslational level by markedly decreasing the activity of mRNA coding for the beta-endorphin/ACTH precursor without any alteration in the processing of this precursor.