Progesterone attenuates depressive behavior of younger and older adult C57/BL6, wildtype, and progesterone receptor knockout mice
Progesterone attenuates depressive behavior of younger and older adult C57/BL6, wildtype, and progesterone receptor knockout mice
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DOI：
10.1016/j.pbb.2011.05.024
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发表时间：
2011-10-01
影响因子：
3.6
通讯作者：
Frye, Cheryl A.
中科院分区：
文献类型：
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作者：
Frye, Cheryl A.
黄体酮可能具有独立于细胞内孕激素受体（PR）的作用来影响抑郁行为。为了研究这一点，我们在强迫游泳测试（FST）中检查了黄体酮（P；10 mg/kg，SC）对小鼠抑郁行为的影响。在实验1中，受试者是4至6个月大的完整或卵巢切除(OVX)雌性和完整或性腺切除(GDX)雄性C57/BL6小鼠。黄体酮可减少年轻的动情期小鼠和 OVX 小鼠的抑郁行为，但雄性小鼠不受 P 的影响。在实验 2 中，受试者是完整的老年（20-28 个月大）C57/BL6 雌性和雄性小鼠。黄体酮可减少老年雌性和雄性 C57/BL6 小鼠的抑郁行为，尽管雄性的影响更大。在实验 3 中，在 4 至 6 个月大、性腺完整的雌性和雄性野生型或 PR 敲除 (PRKO) 小鼠中检查了 P 的影响。黄体酮降低了年轻成年小鼠、野生型小鼠和 PRKO 小鼠的抑郁行为，这些小鼠比野生型小鼠表现出更大的不动性。在实验 4 中，受试者是 18-24 个月大的野生型或 PRKO 小鼠（实验 4）。黄体酮降低了野生型和 PRKO 小鼠的不动性（它们的基线抑郁行为没有差异）。这些数据共同表明，P 可以降低年轻和老年 C57/BLE、野生型和 PRKO 小鼠的抑郁行为，这表明 P 的急性抗抑郁作用可能独立于“经典”PR 的作用而发生。 (C) 2011 Elsevier Inc. 保留所有权利。
Progesterone may have actions independent of intracellular progestin receptors (PRs) to influence depressive behavior. To investigate this, we examined effects of progesterone (P; 10 mg/kg, SC) on the depressive behavior of mice in the forced swim test (FST). In Experiment 1, subjects were 4 to 6 months old, intact or ovariectomized (OVX) female and intact or gonadectomized (GDX) male, C57/BL6 mice. Progesterone reduced depressive behavior of young diestrous and OVX mice but male mice were impervious to effects of P. In Experiment 2, subjects were intact aged (20-28 months old) C57/BL6 female and male mice. Progesterone reduced depressive behavior of aged female and male C57/BL6 mice, albeit effects were greater among males. In Experiment 3, effects of P were examined in 4 to 6 months old, gonadally-intact, female and male mice that were wildtype or PR knockouts(PRKOs). Progesterone decreased depressive behavior of young adult, wildtype and PRKO mice, which showed greater immobility than did their wildtype counterparts. In Experiment 4, subjects were 18-24 months old wildtype or PRKO mice (Exp 4). Progesterone decreased immobility among wildtype and PRKO mice (which were not different in terms of their baseline depressive behavior). Together these data demonstrate that P decreases depressive behavior of young and older adult C57/BLE, wildtype and PRKO mice, which suggest that acute anti-depressant effects of P may occur independent of actions at "classic" PRs. (C) 2011 Elsevier Inc. All rights reserved.