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Updated: Oct 15, 2025

A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice
Published on: May 15, 2019
Behavioral and Neurochemical Changes in Rats with Recurrent Depression induced by chronic unpredictable stress
Cheng Hong1, Libing Chen1, Weiyue Kong1
1Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Objectives:
The mechanism of recurrent depression remains unclear. This study aimed to evaluate the behavioural and neurochemical patterns of rats with recurrent depression.
Materials And Methods:
An animal model of recurrent depression was established using chronic unpredictable stress and imipramine hydrochloride. The behaviour of the rats was tested during the first onset and recurrence periods of depression. The levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), and cyclic adenosine monophosphate (cAMP) in serum were detected by ELISA. The protein expressions of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) in the hippocampal dentate gyrus (DG) area of rats were detected by western blotting.
Results:
The weight and sugar preference of the rats with recurrent depression were significantly decreased, and the immobility time of tail suspension was significantly increased during the first onset and recurrence periods. The modelling time of rats was shortened by one week in the recurrence period compared with that in the first onset. The model rats with recurrent depression had significantly increased ACTH and CORT and significantly decreased cAMP, CREB, and BDNF levels.
Conclusion:
Rats with recurrent depression are highly susceptible to stress and exhibit depression-like behaviours such as weight loss, increased immobility time in tail suspension test, and reduced sucrose preference index. Moreover, the modelling time was shortened by one week, indicating an obvious susceptibility to recurrent depression. The significantly up-regulated neuroendocrine in the HPA and the significantly inhibited BDNF and protein expression factors in related signalling pathways may be involved in the increased susceptibility to recurrent depression.
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