ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience1998
Withdrawal from 3alpha-OH-5alpha-pregnan-20-One using a pseudopregnancy model alters the kinetics of hippocampal GABAA-gated current and increases the GABAA receptor alpha4 subunit in association with increased anxiety.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
What it found
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Who cites it
104 citing papers in PubMed, 352 citations in OpenAlex.
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- Influence of mirtazapine on plasma concentrations of neuroactive steroids in major depression and on 3alpha-hydroxysteroid dehydrogenase activity.Molecular psychiatry · 2006Trial
- Response to flumazenil in the late luteal phase and follicular phase of the menstrual cycle in healthy control females.Psychopharmacology · 2004Trial
- Molecular Mechanisms of Menstrual Cycle-Related Suicide Risk: A Selective Review of Promising Candidate Systems.Biological psychiatry · 2026Review
- The role of neuroactive steroids in psychiatric and neurological disorders: Neurobiology and therapeutic perspectives.Neuroscience and biobehavioral reviews · 2025Review
- Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders.Life (Basel, Switzerland) · 2024Review
- Isoallopregnanolone Inhibits Estrus Cycle-Dependent Aggressive Behavior.Biomolecules · 2023Article
- Article
- Towards understanding the biology of premenstrual dysphoric disorder: From genes to GABA.Neuroscience and biobehavioral reviews · 2023Review
- The impact of the ovarian cycle on anxiety, allopregnanolone, and corticotropin releasing hormone changes after motherhood in female rats and women.Translational psychiatry · 2023Article
- Role of allopregnanolone-mediated γ-aminobutyric acid A receptor sensitivity in the pathogenesis of premenstrual dysphoric disorder: Toward precise targets for translational medicine and drug development.Frontiers in psychiatry · 2023Review
- Sex-dependent differences in the anxiolytic-like effect of cannabidiol in the elevated plus-maze.Journal of psychopharmacology (Oxford, England) · 2022Article
- Structural, functional, and behavioral significance of sex and gonadal hormones in the basolateral amygdala: A review of preclinical literature.Alcohol (Fayetteville, N.Y.) · 2022Review
- GABA System Modifications During Periods of Hormonal Flux Across the Female Lifespan.Frontiers in behavioral neuroscience · 2022Review
- Considerations of Timing Post-ovariectomy in Mice and Rats in Studying Anxiety- and Depression-Like Behaviors Associated With Surgical Menopause in Women.Frontiers in behavioral neuroscience · 2022Article
- Prenatal Exposure to Bisphenols and Phthalates and Postpartum Depression: The Role of Neurosteroid Hormone Disruption.The Journal of clinical endocrinology and metabolism · 2021Article
- Effect of Estrous Cycle on Behavior of Females in Rodent Tests of Anxiety.Frontiers in psychiatry · 2021Review
- Allopregnanolone in premenstrual dysphoric disorder (PMDD): Evidence for dysregulated sensitivity to GABA-A receptor modulating neuroactive steroids across the menstrual cycle.Neurobiology of stress · 2020Article
- Allopregnanolone-based treatments for postpartum depression: Why/how do they work?Neurobiology of stress · 2019Article
- Neurosteroid regulation of GABABrain research · 2019Review
44 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
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 5alpha-reductase blocker to a pseudopregnant animal, suggesting that it is the GABAA-modulatory 3alpha-OH-5alpha-pregnan-20-one (3alpha, 5alpha-THP) that produces anxiogenic withdrawal symptoms. Twenty-four hours after steroid withdrawal, the time constant for decay of GABAA-gated current was also reduced sixfold, assessed using whole- cell patch-clamp procedures on pyramidal neurons acutely dissociated from CA1 hippocampus. Thus, 3alpha,5alpha-THP withdrawal results in a marked decrease in total GABAA current, a possible mechanism for its anxiogenic, proconvulsant sequelae. In addition, 3alpha,5alpha-THP withdrawal resulted in insensitivity to the normally potentiating effect of the benzodiazepine lorazepam (LZM) on GABAA-gated Cl- current. This withdrawal profile is similar to that reported for other GABAA-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 alpha4 subunit of the GABAA receptor, respectively, in hippocampus. The pseudopregnancy paradigm may be a useful model for periods of endogenous 3alpha,5alpha-THP withdrawal such as premenstrual syndrome and postpartum or postmenopausal dysphoria, when increased emotional lability and BDZ insensitivity have been reported.
Indexed as
Identifiers
9651210PMC6793484W1771372085What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.