Mechanisms underlying CSC-induced breakdown of HPA axis functions

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Chronic psychosocial stress is an acknowledged risk factor for the development of various somatic and affective disorders. There is growing evidence that stress-induced hypo- rather than hypercorticism is causally involved in the pathogenesis of these disorders. We could show that 19 days of chronic subordinate colony housing (CSC), an established and clinically relevant chronic psychosocial stressor for male mice, results in insufficiently working adrenals. Preliminary data indicate that chronic psychosocial stress affects also higher levels of the hypothalamo-pituitary-adrenal (HPA) axis including brain regions involved in negative feedback inhibifion. In the current project we aim to dissect the detailed mechanisms underlying the CSC-induced breakdown of HPA axis functions at the levels of the adrenal glands, pituitary, hypothalamus, and hippocampus. We will use macroscopic, microscopic and molecular techniques, both in vivo and in vitro, to investigate whether and to what extent CSC induces structural and/ or functional changes at these different levels of the HPA axis including glucocorticoid (GC) feedback regulation. To detect possible body side-specific and duration-dependent effects, respectively, these parameters will be assessed at the left and right body side separately at different time points during the CSC exposure. In order to reveal gene x stress environment interactions, selected CSC-relevant parameters will be analysed in mice selectively bred for either differences in stress reactivity or differences in trait anxiety.