{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:45:08Z","timestamp":1791585908736,"version":"4.3.4"},"reference-count":168,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T00:00:00Z","timestamp":1622678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Israel Academy of Science and Humanities","award":["1174\/14"],"award-info":[{"award-number":["1174\/14"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Previously, we found that basal corticosterone pulsatility significantly impacts the vulnerability for developing post-traumatic stress disorder (PTSD). Rats that exhibited PTSD-phenotype were characterized by blunted basal corticosterone pulsatility amplitude and a blunted corticosterone response to a stressor. This study sought to identify the mechanisms underlining both the loss of pulsatility and differences in downstream responses. Serial blood samples were collected manually via jugular vein cannula at 10-min intervals to evaluate suppression of corticosterone following methylprednisolone administration. The rats were exposed to predator scent stress (PSS) after 24 h, and behavioral responses were assessed 7 days post-exposure for retrospective classification into behavioral response groups. Brains were harvested for measurements of the glucocorticoid receptor, mineralocorticoid receptor, FK506-binding protein-51 and arginine vasopressin in specific brain regions to assess changes in hypothalamus\u2013pituitary\u2013adrenal axis (HPA) regulating factors. Methylprednisolone produced greater suppression of corticosterone in the PTSD-phenotype group. During the suppression, the PTSD-phenotype rats showed a significantly more pronounced pulsatile activity. In addition, the PTSD-phenotype group showed distinct changes in the ventral and dorsal CA1, dentate gyrus as well as in the paraventricular nucleus and supra-optic nucleus. These results demonstrate a pre-trauma vulnerability state that is characterized by an over-reactivity of the HPA and changes in its regulating factors.<\/jats:p>","DOI":"10.3390\/ijms22116050","type":"journal-article","created":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T10:59:51Z","timestamp":1622717991000},"page":"6050","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Is PTSD-Phenotype Associated with HPA-Axis Sensitivity? Feedback Inhibition and Other Modulating Factors of Glucocorticoid Signaling Dynamics"],"prefix":"10.3390","volume":"22","author":[{"given":"Dor","family":"Danan","sequence":"first","affiliation":[{"name":"Anxiety and Stress Research Unit, Beer-Sheva Mental Health Center, Ministry of Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84170, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doron","family":"Todder","sequence":"additional","affiliation":[{"name":"Anxiety and Stress Research Unit, Beer-Sheva Mental Health Center, Ministry of Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84170, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Zohar","sequence":"additional","affiliation":[{"name":"Post-Trauma Center, Sheba Medical Center, Tel Aviv 52621, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagit","family":"Cohen","sequence":"additional","affiliation":[{"name":"Anxiety and Stress Research Unit, Beer-Sheva Mental Health Center, Ministry of Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84170, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0193-953X(01)00009-0","article-title":"The neurobiology and neuroendocrinology of stress","volume":"25","author":"McEwen","year":"2002","journal-title":"Psychiatr. 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