Stress Response and Drug Metabolism in Mice

A modified stress model was studied to investigate the relationship between the stress response and drug metabolism in mice. Stress was induced in male CD-1 mice by a daily i.p. injection of hypertonic (1.5 M) saline for up to 3 days, whereas control animals received isotonic (0.15 M) saline. Two hours after receiving the saline injection on the first, second, and third day, animals were euthanized, and serum corticosterone (CORT) and liver aminopyrine N-demethylase (AD) and aniline hydroxylase (AH) activities were determined. To detect any effect of osmotic stimulation, a second control group was given 1.5 M saline as drinking water. There was no difference in CORT levels, AD activity, or AH activity between untreated animals and 0.15 M saline treatment. Intra-peritoneal injection of 1.5 M saline markedly increased serum CORT concentrations compared to 0.15 M saline regardless of the duration of the treatment. Injection of 1.5 M saline also decreased both hepatic enzyme activities each time point. Osmotic stimulation alone by hypertonic drinking water had no significant effect on CORT levels, AD activity, or AH activity. In another series of experiments, intact, sham-operated, and adrenalectomized mice were exposed to the stress model. Injected hypertonic saline decreased AD and AH activities in intact and sham-operated animals compared to isotonic saline-treated animals but both enzyme activities were reduced after adrenalectomy regardless of saline treatment used. In conclusion, a suitable model was established to study the interactions between the stress response and the hepatic drug metabolism in mice.