STRESS-RESPONSE AND DRUG-METABOLISM IN MICE

A modified stress model was studied to investigate the relationship be tween the stress response and drug metabolism in mice, Stress was indu ced in male CD-1 mice by a daily ip injection of hypertonic (1.5 M) sa line for up to 3 days, whereas control animals received isotonic (0.15 M) saline. Two hours after receiving the saline injection on the firs t, second, or third day, animals were euthanized, and serum corticoste rone (CORT) and liver aminopyrine N-demethylase (AD) and aniline hydro xylase (AH) activities were determined. To detect any effect of osmoti c stimulation, a second control group was given 1.5 M saline as drinki ng water. There was no difference in CORT levels, AD activity, or AH a ctivity between untreated animals and 0.15 M saline treatment. Intrape ritoneal injection of 1.5 M saline markedly increased serum CORT conce ntrations compared to 0.15 M saline regardless of the duration of the treatment. Injection of 1.5 M saline also decreased both hepatic enzym e activities at each time point. Osmotic stimulation alone by hyperton ic drinking water had no significant effect on CORT levels, AD activit y, or AH activity. In another series of experiments, intact, sham-oper ated, and adrenalectomized mice were exposed to the stress model. Inje cted hypertonic saline decreased AD and AH activities in intact and sh am-operated animals compared to isotonic saline-treated animals but bo th enzyme activities were reduced after adrenalectomy regardless of sa line treatment used. In conclusion, a suitable model was established t o study the interactions between the stress response and the hepatic d rug metabolism in mice. (C) 1996 Society of Toxicology