Abstract

To gain deeper insight into the consequences of corticotropin-releasing hormone (CRH) system hyperactivity, as observed in human affective disorders including major depression, we generated a mouse model which allows the conditional CRH overexpression from the ROSA26 locus (COR). Combining the knock-in of the murine CRH cDNA into the ROSA26 locus with the Cre/loxP system enabled us to overexpress CRH in a spatially regulated fashion at different dosages. Subsequently, two different mouse lines were established where CRH overexpression was either restricted to the central nervous system (CNS, COR-Nes) or even more specifically to the anterior forebrain including structures of the limbic system (COR-Cam). Site-specific overexpression of CRH resulted in alterations within the central CRH/CRH receptor system and affected the regulation of the hypothalamic pituitary adrenocortical (HPA) axis. Furthermore, CRH overexpression resulted in significant behavioural changes in these animals compared to control mice when tested in different behavioural paradigms. The observed alterations were depending on the level and pattern of CRH overexpression.

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