Stress Response and Drug Metabolism in Mice

Abstract

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 ip injection of hypertonic (1.5M) saline for up to 3 days, whereas control animals received isotonic (0.15M) saline. Two hours after receiving the saline injection on the first, second, or third day, animals were euthanized, and serum corticosterone (CORT) and liver aminopyrineN-demethylase (AD) and aniline hydroxylase (AH) activities were determined. To detect any effect of osmotic stimulation, a second control group was given 1.5Msaline as drinking water. There was no difference in CORT levels, AD activity, or AH activity between untreated animals and 0.15Msaline treatment. Intraperitoneal injection of 1.5Msaline markedly increased serum CORT concentrations compared to 0.15Msaline regardless of the duration of the treatment. Injection of 1.5Msaline also decreased both hepatic enzyme activities at 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.