Kappa opioid-induced diuresis in female vs. male rats

Kappa opioid agonists may produce dissimilar discriminative and analgesic effects in female vs. male subjects. The present study was conducted to determine 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), U50,488 (0.3-10 mg/kg), (-)-bremazocine (0.001-0.1 mg/kg) and (-)-pentazocine (1-10 mg/kg), as well as a nonopioid diuretic, furosemide (1-10 mg/kg) produced significantly greater diuresis in normally hydrated, age-matched males than females; however, there was no sex difference in the diuretic effect of butorphanol (0.3-3.0 mg/kg), or in the antidiuretic effect of the mu agonist morphine (1.0-5.6 mg/kg, in water-loaded rats). In contrast, when data were corrected for individual difference in body weight, U69,593, U50,488, (-)-bremazocine, (-)-pentazocine, and furosemide produced nearly equivalent 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 effects were dose-dependently antagonized by the kappa antagonist nor-binaltorphimine in both sexes, indicating a common, kappa receptor-mediated mechanism of action. (-)-Bremazocine was slightly more potent in suppressing vasopressin in 24-h water-deprived males than females. These results suggest that the greater diuretic effects of kappa receptor-selective opioid agonists in male rats are primarily due to males' larger body size (greater body water) relative to age-matched females, but may also be attributed to slightly greater vasopressin suppression in males.