{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T15:25:20Z","timestamp":1780759520866,"version":"3.54.1"},"reference-count":56,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIAAA-R01-AA024095"],"award-info":[{"award-number":["NIAAA-R01-AA024095"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F31 DA054781"],"award-info":[{"award-number":["F31 DA054781"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bowles Center for Alcohol Studies at the University of North Carolina at Chapel Hill","award":["NIAAA-R01-AA024095"],"award-info":[{"award-number":["NIAAA-R01-AA024095"]}]},{"name":"Bowles Center for Alcohol Studies at the University of North Carolina at Chapel Hill","award":["F31 DA054781"],"award-info":[{"award-number":["F31 DA054781"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The neurosteroid 3\u03b1,5\u03b1-THP is a potent GABAA receptor-positive modulator and its regulatory action on the HPA axis stress response has been reported in numerous preclinical and clinical studies. We previously demonstrated that 3\u03b1,5\u03b1-THP down-regulation of HPA axis activity during stress is sex-, brain region- and stressor-dependent. In this study, we observed a deleterious submersion behavior in response to 3\u03b1,5\u03b1-THP (15 mg\/kg) during forced swim stress (FSS) that led us to investigate how 3\u03b1,5\u03b1-THP might affect behavioral coping strategies engaged in by the animal. Given the well-established involvement of the opioid system in HPA axis activation and its interaction with GABAergic neurosteroids, we explored the synergic effects of 3\u03b1,5\u03b1-THP\/opiate system activation in this behavior. Serum \u03b2-endorphin (\u03b2-EP) was elevated by FSS and enhanced by 3\u03b1,5\u03b1-THP + FSS. Hypothalamic Mu-opiate receptors (MOP) were increased in female rats by 3\u03b1,5\u03b1-THP + FSS. Pretreatment with the MOP antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP; 2 mg\/kg, IP) reversed submersion behavior in males. Moreover, in both males and females, CTAP pretreatment decreased immobility episodes while increasing immobility duration but did not alter swimming duration. This interaction between 3\u03b1,5\u03b1-THP and the opioid system in the context of FSS might be important in the development of treatment for neuropsychiatric disorders involving HPA axis activation.<\/jats:p>","DOI":"10.3390\/biom13081205","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T09:06:44Z","timestamp":1690880804000},"page":"1205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Deleterious Interaction between the Neurosteroid (3\u03b1,5\u03b1)3-Hydroxypregnan-20-One (3\u03b1,5\u03b1-THP) and the Mu-Opioid System Activation during Forced Swim Stress in Rats"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7328-3943","authenticated-orcid":false,"given":"Giorgia","family":"Boero","sequence":"first","affiliation":[{"name":"Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, 3027 Thurston Bowles Bldg., CB 7178, Chapel Hill, NC 27599, USA"},{"name":"Department of Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minna H.","family":"McFarland","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, 3027 Thurston Bowles Bldg., CB 7178, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan E.","family":"Tyler","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, 3027 Thurston Bowles Bldg., CB 7178, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8723-734X","authenticated-orcid":false,"given":"Todd K.","family":"O\u2019Buckley","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, 3027 Thurston Bowles Bldg., CB 7178, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha L.","family":"Ch\u00e9ry","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, 3027 Thurston Bowles Bldg., CB 7178, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7540-3363","authenticated-orcid":false,"given":"Donita L.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, 3027 Thurston Bowles Bldg., CB 7178, Chapel Hill, NC 27599, USA"},{"name":"Department of Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Besheer","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, 3027 Thurston Bowles Bldg., CB 7178, Chapel Hill, NC 27599, USA"},{"name":"Department of Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Leslie","family":"Morrow","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, 3027 Thurston Bowles Bldg., CB 7178, Chapel Hill, NC 27599, USA"},{"name":"Department of Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"},{"name":"Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1042\/bj0321957","article-title":"The isolation of progesterone and 3:20-allopregnanolone from ox adrenals","volume":"32","author":"Beall","year":"1938","journal-title":"Biochem. 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