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 journalArticlepeer-review

12 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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