Original Research
Exp. Biol. Med.
Sec. Pharmacology and Toxicology
Volume 250 - 2025 | doi: 10.3389/ebm.2025.10550
This article is part of the Issue2024 International Conference on Neuroprotective Agents Conference ProceedingsView all 12 articles
Comparative electrophysiological study of neuroactive steroid-induced hypnosis in mice: sex and drug-specific differences
Abigail Martin1
Ian Coulter1Reginald Cox1Douglas F Covey2
Slobodan M Todorovic1,3
Tamara Timic Stamenic1*- 1Department of Anesthesiology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- 2Department of Developmental Biology, School of Medicine, Washington University in St. Louis, St Louis, Missouri, United States
- 3Graduate School, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
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Since the discovery of their anesthetic effects, some neuroactive steroids have been used as general anesthetics. However, their effects on thalamocortical oscillations and potential sex differences that are associated with their hypnotic/sedative effects are not well studied. Here, we investigated spectral characteristics and sex differences in hypnotic effect of two common neuroactive steroids: Allopregnanolone (AlloP) and its synthetic analog Alphaxalone (Alpx) in wild type mice using behavioral testing (loss of righting reflex - LORR) and in vivo electrophysiology. Our data revealed sex-differences in LORR duration with 100 mg/kg intraperitoneally injected AlloP and Alpx confirming that females are more sensitive to neuroactive steroid-induced hypnosis. Spectral analysis, thalamocortical and corticocortical phase synchronization showed notable differences between two neuroactive steroids. AlloP induced a profound reduction in local field potential (LFP) and electroencephalogram (EEG) after LORR with higher LFP/EEG suppression in females during first 60 minutes after injection. Also, we observed a decrease in thalamocortical synchronization in lower (delta, theta, alpha) and increase in higher low gamma frequency in AlloP group; similar effects were observed in Alpx treated animals with no change in delta thalamocortical phase locking values. Synchronization between right and left cortex was reduced in all frequencies except low gamma in AlloP-treated group. Similarly, Alpx induced reduction in corticocortical synchronization for theta, alpha and beta frequencies. We conclude that AlloP and Alpx have distinct electrophysiological signatures in thalamocortical circuitry that may underly their sedative/hypnotic effects.
Keywords: neuroactive steroids, hypnosis, electroencephalogram, phase locking value, sex-differences
Received: 25 Feb 2025; Accepted: 30 May 2025.
Copyright: © 2025 Martin, Coulter, Cox, Covey, Todorovic and Timic Stamenic. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Tamara Timic Stamenic, Department of Anesthesiology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, Colorado, United States
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