Indomethacin affects the development of tolerance to ethanol-induced diuresis.

The present study analyzes the effect of indomethacin on the development of tolerance to the diuretic effect of ethanol. Male Wistar rats were treated with ethanol (2 g kg-1 day-1, ip) over a period of 4 weeks and the effect of ethanol on diuresis was assessed weekly. A significant tolerance to the diuretic effect of ethanol was detected after 3 weeks of treatment. However, rats treated simultaneously with ethanol plus indomethacin (5 mg/kg, ip, on alternate days) showed no tolerance to ethanol even after 4 weeks of treatment. The fact that indomethacin prevented the development of tolerance to the diuretic effect of ethanol but had no influence on diuresis per se suggests that prostaglandins play a significant role in the mechanisms of tolerance to ethanol.