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Research Paper|Volume 12, Issue 23|pp 24357—24370

A forced swim-based rat model of premenstrual depression: effects of hormonal changes and drug intervention

Sheng Wei1,2,3, Xiwen Geng2,3, Zifa Li3, Kaiyong Xu3, Minghui Hu2,3, Hongyun Wu4, Wei Shi5, Mingqi Qiao2
  • 1Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Ji’nan 250012, China
  • 2Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Ji’nan 250355, China
  • 3Experimental Center, Shandong University of Traditional Chinese Medicine, Ji’nan 250355, China
  • 4Department of Encephalopathy, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji’nan 250011, China
  • 5Department of Gynecology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji’nan 250011, China
* Equal contribution
Received: June 3, 2020Accepted: September 20, 2020Published: November 21, 2020
https://doi.org/10.18632/aging.202249

Copyright: © 2020 Wei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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 GABAA 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.