Comparative electrophysiological study of neuroactive steroid-induced hypnosis in mice: sex and drug-specific differences
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...
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Frontiers Media S.A.
2025-06-01
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| Series: | Experimental Biology and Medicine |
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| Online Access: | https://www.ebm-journal.org/articles/10.3389/ebm.2025.10550/full |
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| author | Abigail Martin Ian Coulter Reginald Cox Douglas F. Covey Douglas F. Covey Slobodan M. Todorovic Slobodan M. Todorovic Tamara Timic Stamenic |
| author_facet | Abigail Martin Ian Coulter Reginald Cox Douglas F. Covey Douglas F. Covey Slobodan M. Todorovic Slobodan M. Todorovic Tamara Timic Stamenic |
| author_sort | Abigail Martin |
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| description | 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 min 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. |
| format | Article |
| id | doaj-art-a49439c8ce7147cbb7b31e2b200d2bb7 |
| institution | OA Journals |
| issn | 1535-3699 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Experimental Biology and Medicine |
| spelling | doaj-art-a49439c8ce7147cbb7b31e2b200d2bb72025-08-20T02:08:57ZengFrontiers Media S.A.Experimental Biology and Medicine1535-36992025-06-0125010.3389/ebm.2025.1055010550Comparative electrophysiological study of neuroactive steroid-induced hypnosis in mice: sex and drug-specific differencesAbigail Martin0Ian Coulter1Reginald Cox2Douglas F. Covey3Douglas F. Covey4Slobodan M. Todorovic5Slobodan M. Todorovic6Tamara Timic Stamenic7Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Developmental Biology, Washington University School of Medicine, Saint Louis, MO, United StatesTaylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, Saint Louis, MO, United StatesDepartment of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesNeuroscience and Pharmacology Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesSince 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 min 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.https://www.ebm-journal.org/articles/10.3389/ebm.2025.10550/fullneuroactive steroidshypnosiselectroencephalogramphase locking valuesex-differences |
| spellingShingle | Abigail Martin Ian Coulter Reginald Cox Douglas F. Covey Douglas F. Covey Slobodan M. Todorovic Slobodan M. Todorovic Tamara Timic Stamenic Comparative electrophysiological study of neuroactive steroid-induced hypnosis in mice: sex and drug-specific differences Experimental Biology and Medicine neuroactive steroids hypnosis electroencephalogram phase locking value sex-differences |
| title | Comparative electrophysiological study of neuroactive steroid-induced hypnosis in mice: sex and drug-specific differences |
| title_full | Comparative electrophysiological study of neuroactive steroid-induced hypnosis in mice: sex and drug-specific differences |
| title_fullStr | Comparative electrophysiological study of neuroactive steroid-induced hypnosis in mice: sex and drug-specific differences |
| title_full_unstemmed | Comparative electrophysiological study of neuroactive steroid-induced hypnosis in mice: sex and drug-specific differences |
| title_short | Comparative electrophysiological study of neuroactive steroid-induced hypnosis in mice: sex and drug-specific differences |
| title_sort | comparative electrophysiological study of neuroactive steroid induced hypnosis in mice sex and drug specific differences |
| topic | neuroactive steroids hypnosis electroencephalogram phase locking value sex-differences |
| url | https://www.ebm-journal.org/articles/10.3389/ebm.2025.10550/full |
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