Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Ji’nan 250012, China.
Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Ji’nan 250355, China.
Aging (Albany NY). 2020 Nov 21;12(23):24357-24370. doi: 10.18632/aging.202249.
Premenstrual dysphoric disorder (PMDD), a form of premenstrual syndrome (PMS), is a severe health disturbance that affects a patient's emotions; it is caused by periodic psychological symptoms, and its pathogenesis remains unclear. As depression-like symptoms are found in a majority of clinical cases, a reliable animal model of premenstrual depression is indispensable to understand the pathogenesis. Herein, we describe a novel rat model of premenstrual depression, based on the forced swimming test, with a regular estrous cycle. The results showed that in the estrous cycle, the depression-like behavior of rats occurred in the non-receptive phase and disappeared in the receptive phase. Following ovariectomy, the depression-like symptoms disappeared and returned after a hormone priming regimen. Moreover, fluoxetine, an anti-depressant, could reverse the behavioral symptoms in these model rats with normal estrous cycle. Further, the model rats showed significant changes in the serum levels of estrogen and progesterone, hippocampal levels of allopregnanolone, 5-hydroxytryptamine, norepinephrine, and γ-aminobutyric acid (GABA), and in the expression of GABA receptor 4α subunit, all of which were reversed to physiological levels by fluoxetine. Overall, we established a reliable and standardized rat model of premenstrual depression, which may facilitate the elucidation of PMS/PMDD pathogenesis and development of related therapies.
经前期烦躁障碍（PMDD），一种经前期综合征（PMS）的形式，是一种严重的健康紊乱，影响患者的情绪；它是由周期性的心理症状引起的，其发病机制尚不清楚。由于大多数临床病例都存在类似抑郁的症状，因此，建立一种可靠的经前期抑郁动物模型对于了解发病机制是必不可少的。在这里，我们描述了一种基于强迫游泳试验的新型经前期抑郁大鼠模型，具有规律的发情周期。结果表明，在发情周期中，大鼠的类似抑郁行为发生在非接受期，而在接受期消失。卵巢切除后，类似抑郁的症状消失，激素预刺激后又恢复。此外，抗抑郁药氟西汀可逆转正常发情周期模型大鼠的行为症状。进一步的研究发现，模型大鼠的血清雌二醇和孕酮水平、海马全异戊烯醇酮、5-羟色胺、去甲肾上腺素和γ-氨基丁酸（GABA）水平以及GABA 受体 4α 亚单位的表达均发生显著变化，这些变化均被氟西汀逆转至生理水平。总的来说，我们建立了一种可靠的、标准化的经前期抑郁大鼠模型，这可能有助于阐明 PMS/PMDD 的发病机制和相关治疗方法的开发。
