Do corticosterone levels predict female depressive-like behavior in rodents?

Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis is often linked to the neurobiology of depression, though the presence and type of this dysregulation is not a consistent finding. Meanwhile, significant sex differences exist regarding depression and the HPA axis. Animal models of depression simulate certain aspects of the human disease and aim to advance our knowledge regarding its neurobiology and discover new antidepressant treatments. Most animal models of depression induce a depressive-like phenotype taking advantage of stressful experimental conditions, that also increase corticosterone, the main stress hormone in rodents. In this review we present inconsistent results in male and female rodents regarding the interaction between the depressive-like behavioral phenotype and corticosterone. In commonly used models, the female depressive-like phenotype in rodents seems significantly less dependent on the stress hormone corticosterone, whereas the male behavioral response is more evident and associates with variations of corticosterone. Further research and clarification of this sex-dependent interaction will have significant ramifications on the improvement of the validity of animal models of depression.