Journal article
GABA A receptor α4 subunit suppression prevents withdrawal properties of an endogenous steroid
Nature (London), v 392(6679), pp 926-929
30 Apr 1998
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The hormone progesterone is readily converted to 3α-OH-5α-pregnan-20-one (3α,5α-THP) in the brains of males and females,. In the brain, 3α,5α-THP acts like a sedative, decreasing anxiety and reducing seizure activity, by enhancing the function of GABA (γ-aminobutyric acid), the brain's major inhibitory neurotransmitter. Symptoms of premenstrual syndrome (PMS), such as anxiety and seizure, susceptibility, are associated with sharp declines in circulating levels of progesterone and, consequently, of levels of 3α,5α-THP in the brain. Abrupt discontinuation of use of sedatives such as benzodiazepines and ethanol can also produce PMS-like withdrawal symptoms. Here we report a progesterone-withdrawal paradigm, designed to mimic PMS and post-partum syndrome in a rat model. In this model, withdrawal of progesterone leads to increased seizure susceptibility and insensitivity to benzodiazepine sedatives through an effect on gene transcription. Specifically, this effect was due to reduced levels of 3α,5α-THP which enhance transcription of the gene encoding the α4 subunit of the GABAA receptor. We also find that increased susceptibility to seizure after progesterone withdrawal is due to a sixfold decrease in the decay time for GABA currents and consequent decreased inhibitory function. Blockade of the α4 gene transcript prevents these withdrawal properties. PMS symptoms may therefore be attributable, in part, to alterations in expression of GABAA receptor subunits as a result of progesterone withdrawal.
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Details
- Title
- GABA A receptor α4 subunit suppression prevents withdrawal properties of an endogenous steroid
- Creators
- Sheryl S Smith - Allegheny University of the Health SciencesQi Hua Gong - Allegheny University of the Health SciencesFu-Chun Hsu - Allegheny University of the Health SciencesRonald S Markowitz - Allegheny University of the Health SciencesJ. M. H ffrench-Mullen - Wilmington UniversityXinshe Li - Allegheny University of the Health SciencesSusan S Smith - [Retired Faculty]
- Publication Details
- Nature (London), v 392(6679), pp 926-929
- Publisher
- Springer Nature
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]
- Web of Science ID
- WOS:000073359900050
- Scopus ID
- 2-s2.0-0032580125
- Other Identifier
- 991019167582704721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Neurosciences