Mecanismes centrals implicats en la facilitació de la resposta de l'eix hipotàlam pituitari adrenal després de situacions d'estrés crònic.

Project Details

Description

In spite of the suggested ralationship between chronic stress and several organic and psychological pathologies, little is known about the central mechanisms controlling the response of the organisms to stressful situations and the capability to adapt to such situations. The hypothalamus-pituitary-adrenal (HPA) axis, given its usefulness as stress marker and their pathological impact, is the best studied physiological system in stress research. This key position has increased after more recent studies showing that CRF, the main secretagogue of ACTH, plays a pivotal role in the neuroendocrine response, but in the control of most behavioural and physiological responses to stressful situations as well. In has been found in rats that chronic exposure to stressors increases the response of the axis to their main stimulatory factors (CRF, ACTH) and reduces the efficacy of negative feedback exerted by glucocorticoids, these changes resulting in a facilitation of the activity of the HPA axis. However, it is not known either the central mechanisms responsible for such facilitation or the degree of similarities between rats and humans with regard to chronic-stress induced changes in the HPA axis. The present work has therefore two main objectives: 1) To demostrate in rats that the central components of the chronic setress-induced facilitation of the HPA aixs might involve CRF and be situated at the level of the amygdala (a complex area essential for the controo of emotions and of the response to stressful situations) and its connections with the paraventricular nucleus (PVN) of the hypotalamus (the origin of the main secretagogues oa ACTH, including CRF); 2) To demonstrate that similar peripheral changes in the HPA axis might be observed in chronically stressed rats, in humans subjected to chronic stress conditions at work (medical residents) and in major depression, and therefore the abnormalities of the HPA axis described in endogenous depression patients might
StatusFinished
Effective start/end date4/10/964/10/99

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