{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:42:32Z","timestamp":1790782952396,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R35GM141802"],"award-info":[{"award-number":["R35GM141802"]}]},{"name":"National Institutes of Health","award":["K01DA055258"],"award-info":[{"award-number":["K01DA055258"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Neuroactive steroids (NAS) have long been recognized for their hypnotic and anesthetic properties in both clinical and preclinical settings. While sex differences in NAS sensitivity are acknowledged, the underlying mechanisms remain poorly understood. Here, we examined sex-specific responses to an endogenous NAS epipregnanolone (EpiP) in wild-type mice using behavioral assessment of hypnosis (loss of righting reflex, LORR) and in vivo electrophysiological recordings. Specifically, local field potentials (LFPs) were recorded from the central medial thalamus (CMT) and electroencephalogram (EEG) signals were recorded from the barrel cortex. We found that EpiP-induced LORR exhibited clear sex differences, with females showing increased sensitivity. Spectral power analysis and thalamocortical (TC) and corticocortical (CC) phase synchronization further supported enhanced hypnotic susceptibility in female mice. Our findings reveal characteristic sex-dependent effects of EpiP on the synchronized electrical activity in both thalamus and cortex. These results support renewed exploration of endogenous NAS as clinically relevant anesthetic agents.<\/jats:p>","DOI":"10.3390\/biom15071033","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T10:33:47Z","timestamp":1752748427000},"page":"1033","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Electrophysiological Characterization of Sex-Dependent Hypnosis by an Endogenous Neuroactive Steroid Epipregnanolone"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2865-5872","authenticated-orcid":false,"given":"Tamara","family":"Timic Stamenic","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Coulter","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas F.","family":"Covey","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, Washington University School of Medicine, Saint Louis, MO 63101, USA"},{"name":"Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, Saint Louis, MO 63101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2613-0391","authenticated-orcid":false,"given":"Slobodan M.","family":"Todorovic","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"Neuroscience and Pharmacology Graduate Program, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/B978-0-444-53630-3.00008-7","article-title":"Neurosteroids: Endogenous Role in the Human Brian and Therapeutic Potentials","volume":"186","author":"Reddy","year":"2010","journal-title":"Prog. 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