SSRIs and the female brain - potential for utilizing steroid-stimulating properties to treat menstrual cycle-linked dysphorias
SSRIs and the female brain - potential for utilizing steroid-stimulating properties to treat menstrual cycle-linked dysphorias
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DOI：
10.1177/0269881113490327
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发表时间：
2013-12-01
影响因子：
4.1
通讯作者：
Lovick, Thelma
中科院分区：
文献类型：
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作者：
Lovick, Thelma
选择性5-羟色胺再摄取抑制剂的一个意想不到的特性是，在远低于影响5-HT系统的剂量下，它们能够提高神经活性类固醇如孕酮代谢物别孕烯醇酮的脑浓度。在女性中，当黄体晚期孕酮分泌急剧下降时，快速停用别孕烯醇酮会导致月经周期相关疾病，如经前综合征和月经性癫痫。短期，低剂量氟西汀在黄体后期有可能防止这种疾病的发展，通过提高脑别孕烯醇酮浓度。在雌性大鼠中，由于卵巢孕酮分泌福尔斯在间情期后期（类似于女性的黄体期后期）迅速下降，停用别孕烯醇酮诱导参与介导焦虑样行为的脑区域中GABA能神经元上的突触外GABA（A）受体上调。这种受体可塑性的功能后果是主要神经元的去抑制、过度兴奋的神经元回路和对焦虑应激的行为反应性增加。这些戒断反应可以通过在发情后期用氟西汀进行短期治疗来预防，氟西汀可以提高大脑中别孕烯醇酮的浓度，从而减缓快速的生理下降。氟西汀的类固醇刺激特性为开发女性月经周期相关疾病的新疗法提供了尚未开发的机会，这些疾病是由脑中别孕烯醇酮浓度的突然福尔斯下降引起的。
One unexpected property of selective serotonin reuptake inhibitors is their ability, at doses well below those that effect 5-HT systems, to raise brain concentrations of neuroactive steroids such as the progesterone metabolite allopregnanolone. In women, rapid withdrawal from allopregnanolone when progesterone secretion drops sharply in the late luteal phase precipitates menstrual cycle-linked disorders such as premenstrual syndrome and catamenial epilepsy. Short-term, low-dose fluoxetine during the late luteal phase has the potential to prevent the development of such disorders, by raising brain allopregnanolone concentration. In female rats, withdrawal from allopregnanolone, as ovarian progesterone secretion falls rapidly in the late diestrus phase (similar to late luteal phase in women), induces upregulation of extrasynaptic GABA(A) receptors on GABAergic neurons in brain regions involved in mediating anxiety-like behaviors. The functional consequence of this receptor plasticity is disinhibition of principal neurons, hyperexcitable neuronal circuitry and increased behavioral responsiveness to anxiogenic stress. These withdrawal responses were prevented by short-term treatment with fluoxetine during the late diestrus phase, which raised brain allopregnanolone concentration, so blunting the rapid physiological fall. The steroid-stimulating properties of fluoxetine offer untapped opportunities for developing new treatments for menstrual cycle-linked disorders in women, which are precipitated by abrupt falls in brain concentration of allopregnanolone.