Behavioral and neurobiological consequences of prolonged glucocorticoid exposure in rats: relevance to depression

Abstract

Stress is a critical environmental trigger for the development of clinical depression, yet little is known about the specific neurobiological mechanisms by which stress influences the development of depressive symptomatology. Animal models provide an efficient way to study the etiology of human disorders such as depression, and a number of preclinical models have been developed to assess the link between stress, glucocorticoids, and depressive behavior. These mode ls typically make use of repeated exposure to physical or psychological stressors in rodents or other small laboratory animals. This review focuses primarily on a recently developed preclinical model of depression that uses exogenous administration of the stress hormone corticosterone (CORT) in rodents instead of exposure to physical or psychological stressors. Repeated CORT administration in rats or mice produces reliable behavioral and neurobiological alterations that parallel many of the core symptoms and neurobiological changes associated with human depression. This provides an opportunity to study behavior and neurobiology in the same animal, so that the neurobiological factors that underlie specific symptoms can be identified. Taken together, these findings suggest that exogenous CORT administration is a useful method for studying the relationship between stress, glucocorticoids, and depression. Further study with this model may provide important new data regarding the neurobiological bases of depression.