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Updated: May 28, 2026
A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice
Published on: May 15, 2019
[Establishment of an gastric dysfunction and depression comorbidity model simulating clinical etiology in mice using
Qingyang Huang1, Wenwen Shen1, Jin Hu1
1College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, China.
Objectives:
To establish a mouse model with the comorbidity of gastric dysfunction and depression mimicking clinical onset of the condition.
Methods:
Thirty male C57BL/6J mice were randomly divided into control, 14-day model, and 28-day model groups (n=10). The mice in the latter two groups were subjected to continuous combined stresses induced by tail clamping, cold-saline gavage and irregular feeding for 14 or 28 days. Gastric motility, gastric emptying and histopathological changes of the mice were evaluated using strain gauge sensors, in vivo imaging and HE staining, respectively, and behavioral tests were used to assess their depression-like behaviors. Serum corticotropin-releasing factor (CRF), brain-derived neurotrophic factor (BDNF), gastrin, motilin, and gastric nitric oxide synthase (NOS) and acetylcholinesterase (AChE) levels were measured by ELISA to explore the peripheral mechanisms.
Results:
Compared with control mice, the mice in 14-day model group exhibited reduced body weight, food intake and gastric motility amplitude with delayed gastric emptying but showed no significant depression-like behaviors; in 28-day model group, these changes were further exacerbated, and significant depression-like behaviors were observed. Compared with 14-day model group, the 28-day model group displayed severer gastric dysfunction and depression-like behaviors. Compared with control group, exposure to complex stresses for 14 days significantly increased serum CRF and decreased BDNF, gastrin and motilin levels, increased gastric NOS and decreased gastric AChE level, which were worsened after a 28-day exposure. HE staining showed no obvious histological changes in the gastric mucosa in the two model groups.
Conclusions:
Combined stresses induced by tail clamping, cold-saline gavage and irregular feeding for 28 days can induced the comorbidity of gastric dysfunction and depression in mice, and abnormal changes in serum neurotransmitters, brain-gut peptides and vagus activity may partly participate in the pathogenesis of the comorbidity.
