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

Ethan H. Beckley; Angela C. Scibelli; Deborah A. Finn

doi:10.1016/j.psyneuen.2010.11.004

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

Ethan H. Beckley
, Angela C. Scibelli
, Deborah A. Finn

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

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.

Original language	English (US)
Pages (from-to)	824-833
Number of pages	10
Journal	Psychoneuroendocrinology
Volume	36
Issue number	6
DOIs	https://doi.org/10.1016/j.psyneuen.2010.11.004
State	Published - Jul 2011

Funding

Major funding was provided by grants AA010760, AA012439, T32-AA07468, F31-MH081560, and F31-AA018043 from the National Institutes of Health, and a Merit Review Grant from the Department of Veterans Affairs. Additional support was provided by the N.L. Tartar Research Fellowship, the American Psychological Foundation/Council of Graduate Departments of Psychology Graduate Research Scholarship, and by the Nancy and Dodd Fischer Scholarship from the ARCS Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health, the National Institute on Alcohol Abuse and Alcoholism, the National Institutes of Health, or other granting agencies. Granting agencies had no further role in experimental design, implementation, analysis, interpretation, or in any other aspect of the experiments reported currently.

Funders	Funder number
American Psychological Foundation/Council
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health
National Institute of Alcohol Abuse and Alcoholism	F31AA018043
U.S. Department of Veterans Affairs
Achievement Rewards for College Scientists Foundation

Keywords

Allopregnanolone
CDB-4124
Forced swim test
Mifepristone
Postpartum depression
Premenstrual syndrome
Progesterone receptors

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Endocrinology
Endocrine and Autonomic Systems
Psychiatry and Mental health
Biological Psychiatry

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10.1016/j.psyneuen.2010.11.004

Cite this

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

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 GABAA 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.",

keywords = "Allopregnanolone, CDB-4124, Forced swim test, Mifepristone, Postpartum depression, Premenstrual syndrome, Progesterone receptors",

author = "Beckley, \{Ethan H.\} and Scibelli, \{Angela C.\} and Finn, \{Deborah A.\}",

note = "Funding Information: Major funding was provided by grants AA010760, AA012439, T32-AA07468, F31-MH081560, and F31-AA018043 from the National Institutes of Health, and a Merit Review Grant from the Department of Veterans Affairs. Additional support was provided by the N.L. Tartar Research Fellowship, the American Psychological Foundation/Council of Graduate Departments of Psychology Graduate Research Scholarship, and by the Nancy and Dodd Fischer Scholarship from the ARCS Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health, the National Institute on Alcohol Abuse and Alcoholism, the National Institutes of Health, or other granting agencies. Granting agencies had no further role in experimental design, implementation, analysis, interpretation, or in any other aspect of the experiments reported currently. ",

year = "2011",

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

Abstract

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Keywords

ASJC Scopus subject areas

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