STUDIES ON ANTIDIURETIC ACTION OF MOPHINE IN RAT

Morphine sulfate (MS) given s.c. or i.v. produces a dose-response related decrease in urine flow in the alcohol-anesthetized-diuresing rat with a bladder fistula. The antidiuretic effect is not seen if the hydrating infusion contains mannitol instead of glucose-saline. These results are compatible with the proposal that the acute antidiuretic effect of morphine is mediated by the release of ADH from the neurohypophysis. Tolerance to the antidiuretic effect of MS rapidly develops in rats treated on an increasing schedule of MS. After 5 days of MS treatment, tolerance to the antidiuretic effect of MS given i.v. or s.c. is nearly complete and the initial response to MS becomes diuretic. At the same time renal sensitivity to Pitressin is unchanged. The development of tolerance to the antidiuretic effect of MS, seen after one or more doses, may be due to a morphine induced blockade of ADH release. © 1968.