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Updated: Jul 17, 2026

The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice
Published on: October 24, 2018
The delayed effects of chronic unpredictable stress on anxiety measures
Leslie Matuszewich1, Jared J Karney, Samantha R Carter
1Department of Psychology, Northern Illinois University, DeKalb, IL 60115, USA. lmatusze@niu.edu
Abstract:
Previous research has found that exposure to unpredictable stress can augment anxiety in humans and animals. The appearance of anxiety symptoms in humans frequently develop after stress exposure has terminated, but few rodent studies have systematically examined the delayed anxiogenic effects of unpredictable stress. Therefore, the current study investigated whether anxiety-like behaviors in rats would increase at several time intervals following exposure to chronic unpredictable stress (CUS). Unconditioned and conditioned response tasks were used to assess anxiety in male rats 1, 7 or 14 days following exposure to 10 days of a variety of stressors. Rats exposed to CUS showed increased burying behaviors and immobility during the defensive burying test, a conditioned anxiety test. The effects on burying behavior were apparent 7 and 14 days after the termination of the unpredictable stress procedure, but not when tested 1 day after CUS. Total time immobile in the defensive burying test also increased 14 days after termination of the last stressor. In contrast, there were no significant effects of CUS on behavioral measures in the unconditioned response tasks, the elevated plus-maze or light-dark box, at any time point following exposure to CUS. The current findings suggest that CUS may be a useful model of human conditioned anxiety that develops subsequent to chronic stress exposure.
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