Effects of fentanyl, injected into the hypothalamic supraoptic and paraventricular nuclei, in a water-loaded and ethanol-anesthetized rat.

The analgesic fentanyl, having a predominantly mu-opioid agonist activity, when injected into the supraoptic or paraventricular nucleus of the hypothalamus in a water-loaded and ethanol-anesthetized rat, induced a potent antidiuretic effect in a time- and dose-dependent manner. The outflow of urine decreased to a minimal level of approximately 5% of the initial control, at 20-40 min and recovered to approximately 80% at 90 min after injection of fentanyl (30 nmol). The median effective dose (ED50) for the antidiuretic effect of fentanyl was approximately 13 nmol, when injected into the supraoptic or paraventricular nucleus, being nearly equipotent with morphine. The osmotic pressure of urine increased up to approximately 200% of control, at the minimal rate of outflow of urine when fentanyl (30 nmol) was injected into the supraoptic or paraventricular nucleus. Transient but significant decreases in mean blood pressure and in rate of respiration were observed when fentanyl (30 nmol) was injected into the supraoptic or paraventricular nucleus. The antidiuretic and the autonomic effects (transient decreases in mean blood pressure and rate of respiration) were inhibited by the previous injection of an opioid receptor antagonist, naloxone (300 or 600 nmol) into the nuclei. The results suggest that the effects of fentanyl were induced through opioid receptors in the nuclei.