Mice with targeted mutations of glucocorticoid and mineralocorticoid receptors: Models for depression and anxiety?

Impaired corticosteroid receptor signaling is a key mechanism in the pathog enesis of stress-related psychiatric disorders such as depression and anxie ty. Since in vivo expression and functional studies of corticosteroid recep tors are not feasible in the human central nervous system, such analyses ha ve to be done in animal models. Transgenic mice with mutations of corticost eroid receptors are promising tools, which allow us to investigate the role of these proteins in the pathogenesis of symptoms characteristic for depre ssion and anxiety. This review summarizes the neuroendocrinological and beh avioral findings that have been obtained in six different mouse strains wit h specific mutations that influence the expression or the function of the g lucocorticoid or the mineralocorticoid receptor (MR). The analyses of these mice helped to define molecular concepts of how corticosteroid receptors r egulate the activity of the hypothalamic-pituitary-adrenal (HPA) system. Fu rthermore, some of these mutant mice exhibited characteristic alterations i n behavioral tests for anxiety and despair. However, so far, none of the mo use strains described here can be viewed as an animal model of a specific p sychiatric disease defined by common diagnostic criteria. Using high throug hput technologies for the identification of genes regulated by glucocortico id receptor (GR) and NM in brain areas responsible for specific symptoms of stress-related disorders will yield potential new drug targets for the tre atment of depression and anxiety. (C) 2001 Elsevier Science Inc. All rights reserved.