Glucocorticoid and mineralocorticoid receptors are involved in the facilitation of anxiety-like response induced by restraint
Glucocorticoid and mineralocorticoid receptors are involved in the facilitation of anxiety-like response induced by restraint
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DOI：
10.1159/000054643
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发表时间：
2001-04-01
影响因子：
4.1
通讯作者：
Volosin, M
中科院分区：
文献类型：
--
作者：
Calvo, N;Volosin, M
在之前的研究中，我们已经表明，暴露于单一不可避免的应激源（15分钟限制）的雄性Wistar大鼠24小时后在高架十字迷宫（EPM）中表现出类似焦虑的行为，通过在应激前3小时用美替拉酮（75 mg/kg i,p.）抑制皮质酮（CS）合成来逆转这种行为。由于 CS 与两种中枢皮质类固醇受体（盐皮质激素 (MR) 和糖皮质激素 (GR) 受体）结合，因此在 EPM 中评估了 MR 和 GR 在调节焦虑反应中的参与情况。在约束前 1 小时，对经过美替拉酮预处理的大鼠给予 GR 激动剂地塞米松（Dex，1.25 微克/千克，皮下注射），可恢复应激源诱导的焦虑样反应。去除肾上腺也抑制了类焦虑作用，这种作用可以通过在应激前 1 小时施用 Dex（1.25 微克/千克，皮下注射）、MR 激动剂脱氧皮质酮（0.8 毫克/千克，皮下注射）或 CS（MR 和 GR 的常见内源性激动剂（5 毫克/千克，皮下注射））来恢复。在抑制选择性 GR 拮抗剂（A-GR，RU 38486，100 ng/2 μl）、选择性 MR 拮抗剂（A-MR，RU 28318，100 ng/2 μl）或 A-GR 和 A-MR 的组合（各 100 ng/2μl）之前 15 分钟，向完整动物脑室内输注，消除了应激诱导的应激反应。类焦虑作用。目前的研究结果表明，MR 和 GR 都参与了约束引起的焦虑反应的长期 CS 调节。两种受体以独立的方式介导 CS 效应。版权所有 (C) 2001 S. Karger AG。巴塞尔。
In previous studies, we have shown that male Wistar rats exposed to a single inescapable stressor session (15 min restraint) exhibited 24 h later an anxiogenic-like behavior in the elevated plus-maze (EPM), which was reversed by inhibition of corticosterone (CS) synthesis with metyrapone (75 mg/kg i,p.) 3 h before stress. Since CS binds to two central corticosteroid receptors, the mineralocorticoid (MR) and the glucocorticoid (GR) receptors, involvement of MR and GR in the modulation of anxiogenic responses was assessed in the EPM. Administration of the GR agonist dexamethasone (Dex, 1.25 mug/kg s.c.) to metyrapone-pretreated rats 1 h before restraint restored the anxiogenic-like response induced by the stressor. Removal of the adrenals also inhibited the anxiogenic-like effect, which was restored by either Dex (1.25 mug/kg s.c.), the MR agonist deoxycorticosterone (0.8 mg/kg s.c.) or CS, the common endogenous agonist of MR and GR (5 mg/kg s.c,) administered 1 h before stress. Intracerebroventricular infusion to intact animals 15 min before restraint of either a selective GR antagonist (A-GR, RU 38486, 100 ng/2 mul), a selective MR antagonist (A-MR, RU 28318, 100 ng/2 mul) or a combination of A-GR and A-MR (100 ng of each one/2 mul), abolished the stress-induced anxiogenic-like effect. The present findings indicate that both MR and GR are involved in the long-term CS modulation of the anxiety response induced by restraint. Both receptors mediate CS effects in an independent manner. Copyright (C) 2001 S. Karger AG. Basel.