Antidiuretic effects of morphine microinjected into the hypothalamic supraoptic and paraventricular nuclei in a water-loaded and ethanol-anesthetized rat.

Effects of morphine microinjected into the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei, which contain neurons producing and releasing antidiuretic hormone (vasopressin), on the outflow and the osmotic pressure of urine and other visceral functions were investigated in a rat which was loaded with water and anesthetized with ethanol. The opioid drug, having predominantly mu-agonist activity, when microinjected into the SON or PVN induced potent antidiuretic effects in dose-dependent and time-dependent manners with no significant effects on the other visceral functions. The approx. ED50 values for morphine were 19 and 9 nmol when it was microinjected into the SON and PVN, respectively. The antidiuretic effects showed slow onset and long duration, with a minimal outflow at approx. 50 min after microinjection and a return to approx. 50% of the initial control value by 1.5 hr. The morphine-induced effects were inhibited by pretreatment with naloxone or atropine, but not inhibited by pretreatment with alpha- or beta-adrenoceptor antagonists, suggesting that the antidiuretic effects were mediated through an opioid receptor having low sensitivity to naloxone and also possibly mediated through a muscarinic receptor which was stimulated probably by the ACh released by morphine.