Allopregnanolone Mediates Affective Switching Through Modulation of Oscillatory States in the Basolateral Amygdala.
Autor: | Antonoudiou P; Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts., Colmers PLW; Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts., Walton NL; Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts., Weiss GL; Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts., Smith AC; Sage Therapeutics, Inc., Cambridge, Massachusetts., Nguyen DP; Sage Therapeutics, Inc., Cambridge, Massachusetts., Lewis M; Sage Therapeutics, Inc., Cambridge, Massachusetts., Quirk MC; Sage Therapeutics, Inc., Cambridge, Massachusetts., Barros L; Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts; Department of Biology, Hamilton College, Clinton, New York., Melon LC; Department of Biology, Wesleyan University, Middletown, Connecticut., Maguire JL; Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts. Electronic address: Jamie.Maguire@tufts.edu. |
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Jazyk: | angličtina |
Zdroj: | Biological psychiatry [Biol Psychiatry] 2022 Feb 01; Vol. 91 (3), pp. 283-293. Date of Electronic Publication: 2021 Jul 27. |
DOI: | 10.1016/j.biopsych.2021.07.017 |
Abstrakt: | Background: Brexanolone (allopregnanolone) was recently approved by the Food and Drug Administration for the treatment of postpartum depression, demonstrating long-lasting antidepressant effects. Despite our understanding of the mechanism of action of neurosteroids as positive allosteric modulators of GABA Methods: We used electroencephalogram recordings in rats and humans along with local field potential, functional magnetic resonance imaging, and behavioral tests in mice to assess the impact of neurosteroids on network states in brain regions implicated in mood and used optogenetic manipulations to directly examine their relationship to behavioral states. Results: We demonstrated that allopregnanolone and synthetic neuroactive steroid analogs with molecular pharmacology similar to allopregnanolone (SGE-516 [tool compound] and zuranolone [SAGE-217, investigational compound]) modulate oscillations across species. We further demonstrated a critical role for interneurons in generating oscillations in the basolateral amygdala (BLA) and a role for δ-containing GABA Conclusions: Our findings demonstrate a novel molecular and cellular mechanism mediating the well-established anxiolytic and antidepressant effects of neuroactive steroids. (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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