Kappa opioid-induced diuresis in female vs. male rats

kappa Opioid agonists may produce dissimilar discriminative and analgesic e ffects in female vs. male subjects. The present study was conducted to dete rmine whether a prototypic physiological effect of kappa agonists-diuresis- also differs between the sexes. When data were not corrected for individual differences in body weight, the kappa agonists U69,593 (0.03-3.0 mg/kg), U 50,488 (0.3-10 mg/kg), (-)-bremazocine (0.001-0.1 mg/kg) and (-)-pentazocin e (1-10 mg/kg), as well as a nonopioid diuretic, furosemide (1-10 mg/kg) pr oduced significantly greater diuresis in normally hydrated, age-matched mal es than females; however, there was no sex difference in the diuretic effec t of butorphanol (0.3-3.0 mg/kg), or in the antidiuretic effect of the mu a gonist morphine (1.0-5.6 mg/kg, in water-loaded rats). In contrast, when da ta were corrected for individual difference in body weight, U69,593, U50,48 8, (-)-bremazocine, (-)-pentazocine, and furosemide produced nearly equival ent diuresis/kg in females and males, whereas butorphanol produced slightly greater diuresis/kg, and morphine produced significantly less antidiuresis /kg, in females than males. U69,593-induced diuresis was highly similar in males and females of similar body weight (i.e., different ages). U69,593 ef fects were dose-dependently antagonized by the kappa antagonist nor-binalto rphimine in both sexes, indicating a common, kappa receptor-mediated mechan ism of action. (-)-Bremazocine was slightly more potent in suppressing vaso pressin in 24-h water-deprived males than females. These results suggest th at the greater diuretic effects of kappa receptor-selective opioid agonists in male rats are primarily due to males' larger body size (greater body wa ter) relative to age-matched females, but may also be attributed to slightl y greater vasopressin suppression in males. (C) 1999 Elsevier Science Inc.