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 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.
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA. beckleye@ohsu.edu
authors.forename: Ethan H
authors.initials: EH
authors.lastname: Beckley
authors.forename: Angela C
authors.initials: AC
authors.lastname: Scibelli
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Finn
mesh_terms: D000818:Animals; D003863:Depression / Q000139:chemically induced* / Q000503:physiopathology; D019052:Depression, Postpartum; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D018120:Finasteride / Q000494:pharmacology / Q000633:toxicity; D008124:Locomotion / Q000187:drug effects; D051379:Mice; D008811:Mice, Inbred DBA; D015735:Mifepristone / Q000494:pharmacology / Q000633:toxicity; D009649:Norpregnadienes / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D011293:Premenstrual Syndrome; D011374:Progesterone / Q000494:pharmacology / Q000502:physiology*; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors* / Q000502:physiology; D016037:Single-Blind Method; D013550:Swimming
chemical_list: D009649:Norpregnadienes; D011980:Receptors, Progesterone; C461063:telapristone acetate; D015735:Mifepristone; D011374:Progesterone; D018120:Finasteride