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Updated: Nov 29, 2025
The Forced Swim Test as a Model of Depressive-like Behavior
Published on: March 2, 2015
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
1Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Ji’nan 250012, China.
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.
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.
