Resumo

The hypothalamus-pituitary-adrenal (HPA) axis activity depends on secretion of corticotrophin-releasing-hormone (CRH) and vasopressin (AVP) from paraventricular nucleus (PVN) of the hypothalamus, which in turn activate the secretion of adrenocorticotrophic hormone (ACTH), the principal stimulator of glucocorticoids secretion. Repeated stress by the same stimulus may induce habituation of corticosterone (CT) response in part by the desensitization of the ACTH response due to down regulation of the anterior pituitary CRH receptors. Feedback regulation of the HPA axis by glucocorticoids is mediated through mineralocorticoid receptor (MR) and glucocorticoid receptor (GR). OBJECTIVE: we investigated if effects of chronic repeated stress on HPA axis activity depend on alteration of GR and/or MR expression in the hippocampus. METHODS: after 1 week of environmental adaptation, male Wistar rats weighing 200-230 g were divided in 3 groups submitted to 1 daily hour of restraint stress at morning (0800-1200 h) by 1, 8 or 15 days. At end of 1st, 8th or 15th day between 1400 and 1600 h blood sample was withdrawn through a jugular catheter implanted one day before. After that, all animals were anesthesized and were perfused to remove its brains. Then, were carried out immunofluorescence procedures for CRH, AVP and FOS protein in the medial parvocelluar region of PVN as well for MR and GR in the ventral subiculum of the hippoccampus. RESULTS: plasma CT was higher in the1st (75.0±7 ng/ml) than 8th (22.4±6 ng/ml) or 15th day (38.7±4 ng/ml), p= 0.0014. Similar response occurred with FOS protein expression that was higher in 1st (97±6 neurons/section) than 8th (25±6 neurons/section) or 15th day (40±14 neurons/section), p= 0.0014. GR expression was higher in the 8th day (358±6 neurons/section) than 1st (248±24 neurons/section) or 15th day (263±31 neurons/section), p= 0.011. There was no diference of CRH, AVP and MR expression between the three groups. CONCLUSION: the repeated restraint stress induced adaptation of HPA axis that seems due at least in part to the increase of GR expression in the ventral subiculum of the hippocampus. This structure is known as source of inhibitory afferents to control CRH neurons in the medial parvocellular neurons of the PVN.