Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA.
Psychoneuroendocrinology. 2011 Jul;36(6):824-33. doi: 10.1016/j.psyneuen.2010.11.004. Epub 2010 Dec 15.
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.
孕激素撤退被认为是经前综合征和产后抑郁症的一个潜在因素。孕激素撤退会诱导小鼠出现强迫游泳试验（FST）不动，即类似抑郁的行为，但特定受体在此效应中的作用尚不清楚。孕激素的 GABA(A)受体调节代谢产物孕烷醇酮在抑郁和焦虑相关行为中的作用已被广泛证实，但孕激素受体的作用却很少受到关注。我们给已经用孕激素预处理五天的小鼠注射经典孕激素受体拮抗剂米非司酮（RU-38486）和特异性孕激素受体拮抗剂 CDB-4124，发现这两种化合物都能可靠、强烈且呈剂量依赖性地诱导 FST 不动。尽管 CDB-4124 增加了 FST 不动，但它并没有抑制在跑步机测试中的初始活动。这些发现表明，孕激素受体活性降低导致了小鼠的抑郁样行为，这与孕激素撤退可能导致经前综合征或产后抑郁症症状的假设一致。
