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Cited by 20Stress Responses and CortisolMaternal Mental Health During Pregnancy and PostpartumNeurotransmitter Receptor Influence on Behavior

Progesterone receptor antagonist CDB-4124 increases depression-like behavior in mice without affecting locomotor ability

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Beckley, Ethan H., Scibelli, Angela C., Finn, Deborah A.·2011·Psychoneuroendocrinology
DOI 10.1016/j.psyneuen.2010.11.004PMC PMC3081939
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Abstract

Progesterone withdrawal has been proposed as an underlying factor in premenstrual syndrome and postpartum depression. Progesterone withdrawal induces forced swim test (FST) immobility in mice, a depression-like behavior, but the contribution of specific receptors to this effect is unclear. The role of progesterone's GABA(A) receptor-modulating metabolite allopregnanolone in depression- and anxiety-related behaviors has been extensively documented, but little attention has been paid to the role of progesterone receptors. We administered the classic progesterone receptor antagonist mifepristone (RU-38486) and the specific progesterone receptor antagonist CDB-4124 to mice that had been primed with progesterone for five days, and found that both compounds induced FST immobility reliably, robustly, and in a dose-dependent fashion. Although CDB-4124 increased FST immobility, it did not suppress initial activity in a locomotor test. These findings suggest that decreased progesterone receptor activity contributes to depression-like behavior in mice, consistent with the hypothesis that progesterone withdrawal may contribute to the symptoms of premenstrual syndrome or postpartum depression.

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Authors
Beckley, E. H., Scibelli, A. C., & Finn, D. A.
Affiliations
Oregon Health & Science University (US)
Corresponding author
Beckley, Ethan H.
ORCID
Beckley, Ethan H.
Venue
Psychoneuroendocrinology
Publisher
Elsevier BV
Published
2011-07
Volume
36
Issue
6
Pages
824-833
ISSN
0306-4530 (ISSN-L)
DOI
10.1016/j.psyneuen.2010.11.004
PMC
PMC3081939
OpenAlex
W2013027425
Cited by
20
References
70
Citations by year
2024: 2 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 1 · 2014: 3 · 2012: 4
FWCI
0.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Psychoneuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Alcohol Abuse and Alcoholism (R01AA012439, F31AA018043, T32 AA07468, AA010760, AA012439, T32AA007468, P60AA010760)
  • National Institute of Mental Health (F31MH081560)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
antiprogestins, mifepristone, progesterone withdrawal, depression-like behavior, locomotor activity, premenstrual syndrome, postpartum depression, GABA-A receptor modulation, allopregnanolone
MeSH terms
Animals, Depression, Disease Models, Animal, Dose-Response Relationship, Drug, Female, Locomotion, Mice, Inbred DBA, Norpregnadienes, Premenstrual Syndrome, Progesterone, Receptors, Progesterone, Swimming, Mifepristone, Single-Blind Method, Finasteride, Depression, Postpartum, Mice

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