Rationale

The absence of ovarian hormones that is characteristic of natural and surgical postmenopause in women is frequently related to such disorders as depression and anxiety. Chronic treatment with the flavonoid chrysin was previously shown to exert antidepressant-like effects in rodents subjected to validate behavioral models. Chrysin has also been shown to have anxiolytic-like properties, but its antidepressant-like effects and mechanism of action in the absence of ovarian hormones remain unknown.

Objectives

To compare the effects of the flavonoid chrysin with the effects of the neurosteroids progesterone and allopregnanolone on depression-like behavior in ovariectomized rats and evaluate the participation of γ-aminobutyric acid-A (GABA_A) receptors in these actions.

Methods

Ovariectomized female Wistar rats were subjected to the locomotor activity test and forced swim test. The animals were assigned to eight treatment groups: vehicle, chrysin (1 mg/kg), progesterone (1 mg/kg), allopregnanolone (1 mg/kg), bicuculline (1 mg/kg), and pretreatment with bicuculline followed by chrysin, progesterone or allopregnanolone, respectively. After the treatments, the rats underwent the behavioral tests.

Results

Chrysin, progesterone, and allopregnanolone increased the latency to the first immobility and decreased the total immobility time in the forced swim test. The number of crossings and the time spent rearing and grooming decreased from the pretest to test sessions in the locomotor activity test. Chrysin, progesterone, and allopregnanolone only prevented the decreases in rearing and grooming. Bicuculline blocked the effects of chrysin, progesterone, and allopregnanolone in both behavioral tests.

Conclusions

These results show that the GABA-binding site at GABA_A receptors participates in the acute antidepressant-like effects of chrysin, similar to neurosteroids, in ovariectomized rats.

中文翻译：

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GABAergic 系统参与强迫游泳试验中白杨素（5,7-二羟基黄酮）的抗抑郁样作用：与神经类固醇的比较

基本原理

女性自然绝经和手术后绝经所特有的卵巢激素的缺乏通常与抑郁和焦虑等疾病有关。先前已证明黄酮类白杨素的慢性治疗在经过验证的行为模型的啮齿动物中发挥抗抑郁样作用。白杨素也被证明具有抗焦虑样特性，但其抗抑郁样作用和在没有卵巢激素的情况下的作用机制仍然未知。

目标

比较黄酮类白杨素与神经甾体黄体酮和别孕酮对去卵巢大鼠抑郁样行为的影响，并评估γ-氨基丁酸-A (GABA _A ) 受体在这些作用中的参与。

方法

切除卵巢的雌性 Wistar 大鼠进行运动活动试验和强迫游泳试验。将动物分配到八个治疗组：媒介物、白杨素（1mg/kg）、黄体酮（1mg/kg）、别孕酮（1mg/kg）、荷包牡丹碱（1mg/kg）和用荷包牡丹碱预处理，然后是白杨素，孕酮或别孕酮，分别。治疗结束后，对大鼠进行行为测试。

结果

在强迫游泳测试中，白杨素、黄体酮和别孕酮增加了第一次不动的潜伏期并减少了总不动时间。在自发活动测试中，从预测试到测试阶段，交叉次数以及饲养和梳理所花费的时间都减少了。白杨素、黄体酮和别孕酮只能防止饲养和梳理的减少。荷包牡丹碱阻断了两种行为测试中白杨素、黄体酮和别孕酮的作用。

结论

这些结果表明 GABA _A受体的 GABA 结合位点参与了白杨素的急性抗抑郁样作用，类似于神经类固醇，在切除卵巢的大鼠中。