A Japanese herbal medicine attenuates anxiety-like behavior through GABAA receptor and brain-derived neurotrophic factor expression in a rat model of premenstrual syndrome
A Japanese herbal medicine attenuates anxiety-like behavior through GABAA receptor and brain-derived neurotrophic factor expression in a rat model of premenstrual syndrome
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DOI：
10.1016/j.jphs.2020.11.003
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发表时间：
2021-01-01
影响因子：
3.5
通讯作者：
Iwasaki, Katsunori
中科院分区：
文献类型：
--
作者：
Iba, Hikari;Watanabe, Takuya;Iwasaki, Katsunori
Inochinohaha白色（IHW）是一种日本草药，用于治疗与经前综合征（PMS）相关的焦虑女性。在这项研究中，我们研究了IHW对经历孕酮戒断（PWD）的大鼠（PMS模型）焦虑样行为的影响。雌性大鼠每天注射孕酮，持续21天。开始注射孕酮后15天，口服IHW的水和乙醇提取物（分别为WE-IHW和EE-IHW）。在最后一次注射孕酮后48小时，在高架十字迷宫中评估了类似于迷宫的行为。PWD诱导焦虑样行为，EE-IHW（300 mg/kg），但不是WE-IHW，显着减弱这种行为。GABA激动剂，地西泮或蝇蕈醇的管理，显着衰减PWD诱导的焦虑样行为。为了研究IHW作用的潜在机制，我们分析了这些大鼠杏仁核中GABA（A）受体的表达。EE-IHW改善了PWD诱导的GABA（A）受体β 2-亚基mRNA的降低，尽管β 2-亚基蛋白没有变化。脑源性神经营养因子（BDNF）已被报道具有抗焦虑作用和增强GABA能突触传递。我们发现EE-IHW以剂量依赖性方式增加BDNF水平。我们的研究结果表明，EE-IHW减弱PWD诱导的焦虑样行为，通过增加GABA（A）受体介导的信号转导，通过增加β 2-亚基和BDNF在杏仁核。(C)2020作者Elsevier B. V.代表日本药理学会制作和主办。
Inochinohaha White (IHW) is a Japanese herbal medicine for treating women with anxiety associated with premenstrual syndrome (PMS). In this study, we examined the effects of IHW on anxiety-like behavior in rats undergoing progesterone withdrawal (PWD), a model for PMS. Female rats were injected daily with progesterone for 21 days. Water and ethanol extracts of IHW (WE-IHW and EE-IHW, respectively) were administered orally 15 days after the initiation of progesterone injections. Anxiety-like behavior in an elevated plus maze was evaluated 48 h after the final injection of progesterone. PWD induced anxiety-like behavior, and EE-IHW (300 mg/kg), but not WE-IHW, significantly attenuated this behavior. Administration of the GABA agonists, diazepam or muscimol, significantly attenuated PWD-induced anxiety-like behavior. To investigate the underlying mechanisms of IHW action, we analyzed GABA(A) receptor expression in the amygdala of these rats. EE-IHW ameliorated the PWD-induced decrease in GABA(A) receptor beta 2-subunit mRNA, although beta 2-subunit protein was unchanged. Brain-derived neurotrophic factor (BDNF) has been reported to have anxiolytic effects and enhance GABAergic synaptic transmission. We found that EE-IHW increased BDNF levels in a dose-dependent manner. Our results suggest that EE-IHW attenuates PWD-induced anxiety-like behavior by increasing GABA(A) receptor-mediated signaling via increases in beta 2-subunit and BDNF in the amygdala. (C) 2020 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.