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Isoallopregnanolone antagonize allopregnanolone-induced effects on saccadic eye velocity and self-reported sedation in humans
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
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2015 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 52, p. 22-31Article in journal (Refereed) Published
Abstract [en]

Allopregnanolone (AP) is an endogenous neurosteroid. It modulates the effect of gamma-amino-butyric acid (GABA) on the GABA type A (GABA(A)) receptor, which leads to increased receptor activity. Since the GABA-system is mainly inhibitory, increased AP activity leads to modulation of neuronal activity. In vitro studies of GABA(A) receptor activity and in vivo animal studies of sedation have shown that AP-induced effects can be inhibited by another endogenous steroid, namely isoallopregnanolone (ISO). In this study we investigated if ISO can antagonize AP-induced effects in healthy female volunteers, via measurements of saccadic eye velocity (SEV) and self-rated sedation. With a single-blind cross-over design, 12 women were studied on three separate occasions; given AP alone or AP in combination with one of two ISO doses. Congruent with previous reports, AP administration decreased SEV and induced sedation and these effects were diminished by simultaneous ISO administration. Also, the ISO effect modulation was seemingly stronger for SEV than for sedation. These effects were observed already at an ISO dose exposure that was approximately half of that of AP. In conclusion, ISO antagonized AP-induced decrease in SEV and self-reported sedation, probably in a non-competitive manner.

Place, publisher, year, edition, pages
2015. Vol. 52, p. 22-31
Keywords [en]
Allopregnanolone, Isoallopregnanolone, Saccadic eye velocity, GABA(A) receptor, Sedation, Premenstrual dysphoric disorder
National Category
Endocrinology and Diabetes Neurosciences
Identifiers
URN: urn:nbn:se:umu:diva-100765DOI: 10.1016/j.psyneuen.2014.10.025ISI: 000349271000004PubMedID: 25459890Scopus ID: 2-s2.0-84922679443OAI: oai:DiVA.org:umu-100765DiVA, id: diva2:807926
Available from: 2015-04-26 Created: 2015-03-09 Last updated: 2023-03-23Bibliographically approved

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Bengtsson, Sara K. S.Nyberg, SigridHedström, HelenaZingmark, ElisabethBäckström, TorbjörnBixo, Marie

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