THE EFFECT OF PROLONGED MORPHINE ADMINISTRATION ON THE IN VIVO AND IN VITRO CONJUGATION OF MORPHINE BY RATS

¹ Department of Pharmacology, College of Medicine, University of Vermont Burlington, Vt.

1. Adrenal cortical hormones or compounds which cause their release bring about an increase in the total TBA values and lipid content of rat livers.

2. The increase in liver lipid does not interfere with detoxification of morphine in vivo.

3. Rats excrete the greatest part of an administered dose of morphine in the conjugated form. As tolerance to the drug develops the amount of morphine appearing in the urine decreases. This decrease is at the expense of the conjugated rather than of the free fraction which remains constant.

4. Liver slices taken from morphine-tolerant rats or from rats that have received adrenal cortical extract for a prolonged period conjugate more morphine in vitro than do slices of normal livers. The possible mechanisms of this increased ability to conjugate morphine are discussed.