{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:45:35Z","timestamp":1792370735145,"version":"4.4.0"},"reference-count":64,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Mental Health","award":["MH 06769801"],"award-info":[{"award-number":["MH 06769801"]}]},{"name":"UAlbany","award":["MH 06769801"],"award-info":[{"award-number":["MH 06769801"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Progestogens\u2019 anti-anxiety and anti-depressive effects and mechanisms are not well-understood. Progestogens are hypothesized to have anti-anxiety and anti-depressive effects on behavior, independent of actions at nuclear progestin receptors (NPRs) and dependent on allopregnanolone (5\u03b1-pregnan-3\u03b1-ol-20-one; 3\u03b1,5\u03b1-THP), a 5\u03b1-reduced, neuroactive metabolite of progesterone (P4). Adult c57 mice in behavioral estrus (proestrus; pro) showed more anti-anxiety-like and anti-depressant-like behavior and higher levels of estradiol (E2), P4, and allopregnanolone in the hippocampus\/amygdala complex. Proestrus c57 &gt; 5\u03b1-reductase knockout (5\u03b1RKO) mice made more central entries in an open field than diestrus c57 and 5\u03b1RKO mice that were not different. Ovariectomized (OVX) c57 mice administered 1, 2, or 4 mg\/kg P4 SC showed dosage-dependent increases in central entries in an open field (more anti-anxiety-like behavior); 5\u03b1RKO mice had maximal increases at 1\u20132 mg\/kg P4. OVX c57 and 5\u03b1RKO mice showed maximum increases in central entries with SC 3\u03b1,5\u03b1-THP (4 mg\/kg), and c57s showed a similar maximal response to P4 (4 mg\/kg), but 5\u03b1RKOs response was half at that dosage. P4 (4 mg\/kg SC to OVX c57 or progestin receptor knockout (PRKO) mice decreased immobility (depression-like behavior) in the forced swim task. Effects of E2 and veh were similar in both groups. Levels of 3\u03b1,5\u03b1-THP in the hippocampus\/amygdala were consistent with effects on central entries in the open field. Levels of brain-derived neurotrophic factor (BDNF) in the hippocampus\/amygdala were greater among E2-primed (0.09 mg\/kg, SC) vs vehicle-administered mice. In sum, adult female mice can be responsive to P4 for anti-anxiety\/anti-depressant-like behavior; such effects may be independent of NPRs but require 5\u03b1-reduction and E2\u2019s priming actions at BDNF in the hippocampus\/amygdala complex.<\/jats:p>","DOI":"10.3390\/ijms26031173","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T11:10:39Z","timestamp":1738149039000},"page":"1173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Progesterone Promotes Anti-Anxiety\/Depressant-like Behavior and Trophic Actions of BDNF in the Hippocampus of Female Nuclear Progesterone Receptor, but Not 5\u03b1-Reductase, Knockout Mice"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8452-296X","authenticated-orcid":false,"given":"Cheryl A.","family":"Frye","sequence":"first","affiliation":[{"name":"Comprehensive Neuropsychological Services, 490 Western Avenue, Albany, NY 12203, USA"},{"name":"Department of Psychology, The University at Albany, 1400 Washington Avenue, Albany, NY 12222, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daina M.","family":"Cleveland","sequence":"additional","affiliation":[{"name":"Comprehensive Neuropsychological Services, 490 Western Avenue, Albany, NY 12203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali","family":"Sadarangani","sequence":"additional","affiliation":[{"name":"Comprehensive Neuropsychological Services, 490 Western Avenue, Albany, NY 12203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer K.","family":"Torgersen","sequence":"additional","affiliation":[{"name":"Comprehensive Neuropsychological Services, 490 Western Avenue, Albany, NY 12203, USA"},{"name":"Department of Psychology, The University at Albany, 1400 Washington Avenue, Albany, NY 12222, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41386-023-01721-1","article-title":"Novel neurosteroid therapeutics for post-partum depression: Perspectives on clinical trials, program development, active research, and future directions","volume":"49","author":"Patterson","year":"2024","journal-title":"Neuropsychopharmacology"},{"key":"ref_2","unstructured":"Cable, J.K., and Grider, M.H. 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