{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T13:49:53Z","timestamp":1767275393701,"version":"build-2065373602"},"reference-count":77,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"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>Endocannabinoids play a role in adaptation to stress and regulate the release of glucocorticoids in stressed and unstressed conditions. We recently found that basal corticosterone pulsatility may significantly impact the vulnerability for developing post-traumatic-stress-disorder (PTSD), suggesting that the endocannabinoid system may contribute to its development. To examine this, we exposed rats to predator scent stress (PSS). Behavioral reactions were recorded seven days post-PSS. Cerebrospinal fluid (CSF) was collected from anesthetized rats shortly after PSS exposure to determine the levels of 2-arachidonoyl glycerol (2-AG) and anandamide (AEA). To correlate between endocannabinoids and corticosterone levels, rats were placed in metabolic cages for urine collection. To assess the levels of endocannabinoids in specific brain regions, rats\u2019 brains were harvested one day after behavioral analysis for staining and fluorescence quantification. Moreover, 2-AG was elevated in the CSF of PTSD-phenotype rats as compared with other groups and was inversely correlated with corticosterone urinary secretion. Eight days post-PSS exposure, hippocampal and hypothalamic 2-AG levels and hippocampal AEA levels were significantly more reduced in the PTSD-phenotype group compared to other groups. We posit that maladaptation to stress, which is propagated by an abnormal activation of endocannabinoids, mediates the subsequent stress-induced behavioral disruption, which, later, reduces neuronal the expression of endocannabinoids, contributing to PTSD symptomology.<\/jats:p>","DOI":"10.3390\/ijms22126416","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T11:00:33Z","timestamp":1623754833000},"page":"6416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Is PTSD-Phenotype Associated with HPA-Axis Sensitivity?: The Endocannabinoid System in Modulating Stress Response in Rats"],"prefix":"10.3390","volume":"22","author":[{"given":"Dor","family":"Danan","sequence":"first","affiliation":[{"name":"Anxiety and Stress Research Unit, Beer-Sheva Mental Health Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Ministry of Health, Beer-Sheva 8461144, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Doron","family":"Todder","sequence":"additional","affiliation":[{"name":"Anxiety and Stress Research Unit, Beer-Sheva Mental Health Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Ministry of Health, Beer-Sheva 8461144, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Zohar","sequence":"additional","affiliation":[{"name":"Post-Trauma Center, Sheba Medical Center, Tel Aviv 5262000, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hagit","family":"Cohen","sequence":"additional","affiliation":[{"name":"Anxiety and Stress Research Unit, Beer-Sheva Mental Health Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Ministry of Health, Beer-Sheva 8461144, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4292","DOI":"10.1210\/en.2005-0610","article-title":"Rapid glucocorticoid-mediated endocannabinoid release and opposing regulation of glutamate and gamma-aminobutyric acid inputs to hypothalamic magnocellular neurons","volume":"146","author":"Di","year":"2005","journal-title":"Endocrinology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8461","DOI":"10.1523\/JNEUROSCI.2279-15.2016","article-title":"Acute Stress Suppresses Synaptic Inhibition and Increases Anxiety via Endocannabinoid Release in the Basolateral Amygdala","volume":"36","author":"Di","year":"2016","journal-title":"J. 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