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Updated: Jan 22, 2026

A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice
Published on: May 15, 2019
[Effects of metformin on depressive behavior in chronic stress rats]
Gai-Fen Li1,2, Ming Zhao2, Tong Zhao2
1Center for Brain Disorders Research, Capital Medical University, Beijing Institute of Brain Disorders, Beijing 100069.
Objective:
To detect the effects of metformin on the depressive-like behaviors in rats.
Methods:
Forty male SD rats were randomly divided into four groups: control group (CON group), metformin group (MET group), model group (CUMS group), model + metformin group (CUMS + MET group), 10 rats in each group. Chronic unpredictable mild stress (CUMS) method was used to establish rat depression model in three weeks. After the model was established successfully, two metformin groups were intraperitoneally injected with metformin (100 mg/kg), while the control group and the model group were injected with the same amount of saline once a day for two weeks. After that, the changes of weight gain, sucrose water preference experiment, forced swimming test, tail suspension immobility test and open field test were detected. The morphological changes of hippocampus were observed by Nissl staining.
Results:
Compared with the control group, the weight gain of rats in CUMS group was significantly slowed down (P<0.05), the sucrose preference rate and the spontaneous activity were significantly reduced (P<0.05), and the immobility time in forced swimming and tail suspension immobility test was significantly prolonged (P<0.05), and the morphological structure of hippocampus was changed, which confirmed the success of CUMS depression model. Compared with CUMS group, metformin treatment had no significant effect on body weight of rats, but it could significantly improve sucrose water intake, immobility time and spontaneous activity of CUMS depression model rats (P<0.05), and improve the abnormal morphological changes of hippocampus in CUMS rats.
Conclusion:
Metformin has a therapeutic benefit against CUMS-induced depression, which provides a new treatment for patients with diabetes mellitus complicated with depression.
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