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 journalArticle

11 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 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.

Original languageEnglish (US)
Pages (from-to)824-833
Number of pages10
JournalPsychoneuroendocrinology
Volume36
Issue number6
DOIs
StatePublished - Jul 2011

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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