Analytic and Interpretational Pitfalls to Measuring Fecal Corticosterone Metabolites in Laboratory Rats and Mice

Minimization and alleviation of stress are generally viewed as desirable aspects of laboratory animal management and use. However, achieving that goal requires an unambiguous and valid measure of stress. Glucocorticoid concentrations are commonly used as a physiologic index of stress. Measurement of glucocorticoids in blood, serum or plasma clearly reflects many types of both acute and chronic stress. However, the rapid rise in concentrations of circulating glucocorticoids that occurs even with relatively simple manipulations such as handling has led to the increased use of fecal glucocorticoid metabolite (FCM) assays, which provide a temporally integrated measure that may allow a more accurate interpretation of chronic stressors. In this review, we consider 3 aspects of glucocorticoids as a measure of stress. First, we discuss the analytic and interpretational pitfalls of using FCM concentrations as an index of stress in mice and rats. Second, we consider evidence that some degree of stress may benefit animals by priming physiologic and behavioral adaptations that render the animals more resilient in the face of stress. Finally, we use 2 situations-social housing and food restriction-to illustrate the concept of hormesis-a biologic phenomenon in which a low dose or intensity of a challenge has a beneficial effect, whereas exposure to high doses or intensities is detrimental.