Corticosteroid receptor transgenic mice: models for depression?

Dysregulations and dysfunctions of corticosteroids and their receptors have been implicated in the pathogenesis of stress-related disorders, in particular in depression. It is currently under debate, however, whether corticosteroid imbalances are a cause or rather a consequence of affective disorders. Corticosteroids exert their effects mainly by two receptors: glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs). We present here analyses made on several strains of mice with targeted mutations of corticosteroid receptors. The results help to understand how corticosteroid receptors regulate the hypothalamic-pituitary-adrenal (HPA) system. Furthermore, first behavioral analyses have indicated that corticosteroid receptor mutant mice show alterations in their emotional behavior. Certain mouse strains with specific alterations of GR or MR expression may represent genetic models of depression or at least have a predisposition to develop a depressive or a depression-resistant state upon exposure to stress. The corticosteroid receptor-regulated target genes to be identified in these models may code for proteins that could represent new drug-targets for the treatment of affective disorders.