{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:10Z","timestamp":1787028550144,"version":"build-2736575974"},"reference-count":58,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006109","name":"VEGA","doi-asserted-by":"publisher","award":["2\/0010\/22"],"award-info":[{"award-number":["2\/0010\/22"]}],"id":[{"id":"10.13039\/501100006109","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006109","name":"VEGA","doi-asserted-by":"publisher","award":["2\/0050\/23"],"award-info":[{"award-number":["2\/0050\/23"]}],"id":[{"id":"10.13039\/501100006109","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Post-traumatic stress disorder (PTSD) is a multifactorial psychological disorder that affects different neurotransmitter systems, including the central CRH system. CRH acts via the CRHR1 and CRHR2 receptors, which exert opposite effects, i.e., anxiogenic or anxiolytic. The aim of this work was to investigate how intranasal administration of the CRHR2-specific agonist urocortin 2 (Ucn2) or urocortin 3 (Ucn3) affects manifestations of PTSD in a single prolonged stress (SPS) animal model of PTSD. Elevated plus maze (EPM) and open field (OF) tests were used to assess anxiety-like behavior. Changes in the gene expressions of CRH, CRHR1, CRHR2, glucocorticoid receptor (GR), and FKBP5 were measured in brain regions (BNST, amygdala, and PVN) responsible for modulating the stress response. The SPS animals spent less time in the OF central zone and were less mobile than the controls; however, the Ucn3 treatment reversed this effect. SPS decreased the GR and FKPB5 mRNA levels in the PVN. Ucn3 suppressed the effect of SPS on FKBP5 mRNA expression in the PVN and increased FKBP5 mRNA in the BNST and PVN compared to the stressed animals. We demonstrate that Ucn3 has the potential to ameliorate anxiety-like behavior in SPS animals and also to affect the neuroendocrine system in the BNST and PVN. In addition, we confirm the important role of CRHR2 signaling in mediating the stress response.<\/jats:p>","DOI":"10.3390\/ijms252211908","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T04:03:24Z","timestamp":1730865804000},"page":"11908","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Single Intranasal Administration of Ucn3 Affects the Development of PTSD Symptoms in an Animal Model"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4643-7040","authenticated-orcid":false,"given":"Andrej","family":"Tillinger","sequence":"first","affiliation":[{"name":"Biomedical Research Center of the Slovak Academy of Sciences, Institute of Experimental Endocrinology, 845 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Zvozilov\u00e1","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine of the Slovak Academy of Sciences, Institute of Experimental Pharmacology & Toxicology, 841 04 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6958-1024","authenticated-orcid":false,"given":"Mojm\u00edr","family":"Mach","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine of the Slovak Academy of Sciences, Institute of Experimental Pharmacology & Toxicology, 841 04 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u013dubica","family":"Horv\u00e1thov\u00e1","sequence":"additional","affiliation":[{"name":"Biomedical Research Center of the Slovak Academy of Sciences, Institute of Experimental Endocrinology, 845 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lila","family":"Dziewiczov\u00e1","sequence":"additional","affiliation":[{"name":"Biomedical Research Center of the Slovak Academy of Sciences, Institute of Experimental Endocrinology, 845 05 Bratislava, Slovakia"},{"name":"Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University Bratislava, 842 15 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2144-0534","authenticated-orcid":false,"given":"Jana","family":"Osack\u00e1","sequence":"additional","affiliation":[{"name":"Biomedical Research Center of the Slovak Academy of Sciences, Institute of Experimental Endocrinology, 845 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109211","DOI":"10.1016\/j.neuropharm.2022.109211","article-title":"Pharmacological strategies for post-traumatic stress disorder (PTSD): From animal to clinical studies","volume":"218","author":"Gasparyan","year":"2022","journal-title":"Neuropharmacology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"109418","DOI":"10.1016\/j.neuropharm.2023.109418","article-title":"Alleviating anxiety and taming trauma: Novel pharmacotherapeutics for anxiety disorders and posttraumatic stress disorder","volume":"226","author":"Singewald","year":"2023","journal-title":"Neuropharmacology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"109529","DOI":"10.1016\/j.neuropharm.2023.109529","article-title":"From recent advances in underlying neurocircuitry of fear and anxiety to promising pharmacotherapies for PTSD: The saga of heart, sex and the developing brain","volume":"232","author":"Dabrowska","year":"2023","journal-title":"Neuropharmacology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1146\/annurev.pharmtox.44.101802.121410","article-title":"CRF and CRF receptors: Role in stress responsivity and other behaviors","volume":"44","author":"Bale","year":"2004","journal-title":"Annu. 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