The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Withdrawal from 3α-OH-5α-Pregnan-20-One Using a Pseudopregnancy Model Alters the Kinetics of Hippocampal GABAA-Gated Current and Increases the GABAAReceptor α4 Subunit in Association with Increased Anxiety
Open accessAbstract
In the present study, we have characterized properties of steroid withdrawal using a pseudopregnant rat model. This paradigm results in increased production of endogenous progesterone from ovarian sources and as such is a useful physiological model. “Withdrawal” from progesterone induced by ovariectomy on day 12 of pseudopregnancy resulted in increased anxiety, as determined by a decrease in open arm entries on the elevated plus maze compared to control rats and pseudopregnant animals not undergoing withdrawal. Similar findings were obtained 24 hr after administration of a 5α-reductase blocker to a pseudopregnant animal, suggesting that it is the GABA A-modulatory 3α-OH-5α-pregnan-20-one (3α,5α-THP) that produces anxiogenic withdrawal symptoms. Twenty-four hours after steroid withdrawal, the time constant for decay of GABA A-gated current was also reduced sixfold, assessed using whole- cell patch-clamp procedures on pyramidal neurons acutely dissociated from CA1 hippocampus. Thus, 3α,5α-THP withdrawal results in a marked decrease in total GABA A current, a possible mechanism for its anxiogenic, proconvulsant sequelae. In addition, 3α,5α-THP withdrawal resulted in insensitivity to the normally potentiating effect of the benzodiazepine lorazepam (LZM) on GABA A-gated Cl−current. This withdrawal profile is similar to that reported for other GABA A-modulatory drugs such as the benzodiazepines (BDZs), barbiturates, and ethanol. These changes were also associated with significant two and threefold increases in both the mRNA and protein for the α4 subunit of the GABA A receptor, respectively, in hippocampus. The pseudopregnancy paradigm may be a useful model for periods of endogenous 3α,5α-THP withdrawal such as premenstrual syndrome and postpartum or postmenopausal dysphoria, when increased emotional lability and BDZ insensitivity have been reported.
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GABAA receptor α4 subunit suppression prevents withdrawal properties of an endogenous steroid
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Neurosteroids: biosynthesis and function of these novel neuromodulators
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Neuroactive steroids: mechanisms of action and neuropsychopharmacological properties
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The expectant brain: adapting for motherhood
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Metadata
- Authors
- Smith, S. S., Gong, Q. H., Li, X., Moran, M. H., Bitran, D., Frye, C. A., & Hsu, F.-C.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1998-07-15
- Volume
- 18
- Issue
- 14
- Pages
- 5275-5284
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W1771372085
- Cited by
- 349
- References
- 63
- FWCI
- 8.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- The paper
- Smith, S. S., Gong, Q. H., Li, X., Moran, M. H., Bitran, D., Frye, C. A., & Hsu, F.-C. (1998). Withdrawal from 3α-OH-5α-Pregnan-20-One Using a Pseudopregnancy Model Alters the Kinetics of Hippocampal GABAA-Gated Current and Increases the GABAAReceptor α4 Subunit in Association with Increased Anxiety. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.18-14-05275.1998
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
