Decreased tolerance to ethanol-induced hypothermia in long-term castrate male rats.

A potential role for central stores of vasopressin in the development of tolerance was studied in the long-term castrate rat. Vasopressin stores in the septal region are known to be dramatically depressed following long-term castration. Sprague-Dawley male rat littermates were castrated at 26 days of age or given a sham surgery. Experiments began when animals reached 130 days of age. Tolerance to the hypothermic effects of ethanol occurred in intact but not castrate animals over the course of six daily IP injections of 3.0 g/kg ethanol. Both groups exhibited tolerance to the length of time needed to return to baseline temperature over the 6 days of ethanol injections. Tolerance to this effect of ethanol was still evident in intact animals but not castrates following another injection of ethanol 1 week later. No tolerance developed to the rebound hyperthermia that occurred in both groups. Blood ethanol levels did not differ significantly between castrate and intact littermates administered a single dose of ethanol. Overall, these results support the hypothesis that endogenous vasopressin is involved in the development of some aspects of tolerance to ethanol.