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 language | English (US) |
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Pages (from-to) | 824-833 |
Number of pages | 10 |
Journal | Psychoneuroendocrinology |
Volume | 36 |
Issue number | 6 |
DOIs | |
State | Published - 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