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Abstract
Impaired corticosteroid receptor signaling is a key mechanism in the pathogenesis
of stress-related psychiatric disorders such as depression and anxiety. Since in vivo
expression and functional studies of corticosteroid receptors are not feasible in
the human central nervous system, such analyses have to be done in animal models.
Transgenic mice with mutations of corticosteroid receptors are promising tools, which
allow us to investigate the role of these proteins in the pathogenesis of symptoms
characteristic for depression and anxiety. This review summarizes the neuroendocrinological
and behavioral findings that have been obtained in six different mouse strains with
specific mutations that influence the expression or the function of the glucocorticoid
or the mineralocorticoid receptor (MR). The analyses of these mice helped to define
molecular concepts of how corticosteroid receptors regulate the activity of the hypothalamic-pituitary-adrenal
(HPA) system. Furthermore, some of these mutant mice exhibited characteristic alterations
in behavioral tests for anxiety and despair. However, so far, none of the mouse strains
described here can be viewed as an animal model of a specific psychiatric disease
defined by common diagnostic criteria. Using high throughput technologies for the
identification of genes regulated by glucocorticoid receptor (GR) and MR in brain
areas responsible for specific symptoms of stress-related disorders will yield potential
new drug targets for the treatment of depression and anxiety.