Antidiuretic effect of morphine and vasopressin in morphine tolerant and non-tolerant rats, differential effects on urine composition

Abstract

Morphine injected i.p. produced a dose-related antidiuresis in rats previously hydrated with distilled water or 0.5% NaCl. The morphine-induced antidiuresis was paralleled by a dose-dependent reduction in the excretion of Na +, K + and Cl −. Morphine injected into the lateral cerebral ventricles also caused antidiuresis and reduced the concentration of Na +, K + and Cl − excreted in the urine. The effects of morphine on urine composition and formation were common to levorphanol, methadone or pentazocine injected i.p. but not dextrorphan or naloxone. In contrast to the effects of morphine and related narcotic analgesics, the i.p. administration of vasopressin produced a graded oliguria comparable to that of morphine, but increased the urinary excretion of Na +, K + and Cl − in the urine dose-relatedly. Morphine given i.p. together with vasopressin i.p. counteracted the changes in urine composition caused by vasopressin. Pretreatment with morphine antagonized the diuresis and changes in urine composition produced by furosemide or acetazolamide. After chronic morphine administration, tolerance developed to the effects of morphine on urine formation. Tolerance to morphine was not crossed to the effects of vasopressin. Prelininary experiments indicated that the acute administration of morphine reduced by about 50% the clearance of endogenous creatinine. Results are discussed in relation to the mechanism of action of narcotic analgesics to produce antidiuresis.