DEVELOPMENT OF TOLERANCE TO ANTIDIURETIC EFFECT OF MORPHINE IN MOUSE

Mice treated for 8 days on a schedule of increasing doses of morphine develop tolerance more rapidly to the analgesic than to the antidiuretic effect. A schedule of treatment consisting of morphine 30 mg/kg b.i.d., the dosage being increased 30 mg/kg/day, produced a decrease in the antidiuretic effect when tested with morphine 30 mg/kg. The response declined 25% after 2 days, 40% after 3 days, and 46% after 4 days of treatment. Antidiuretic tolerance occurred concomitantly with an increase in sodium but not potassium excretion. Morphine treatment resulted in an immediate decrease of about 50% in daily food and water consumption accompanied by a decrease in body weight, while daily urine excretion was increased. The development of tolerance to morphine antidiuresis did not appear to be due to a depletion of pituitary vasopressin or a change in renal sensitivity to Pitressin. © 1968.