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Updated: Apr 27, 2026

The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice
Published on: October 24, 2018
Neurochemical and behavioral effects of chronic unpredictable stress
Leslie Matuszewich1, Lisa M McFadden, Ross D Friedman
1aDepartment of Psychology, Northern Illinois University, DeKalb, Illinois bDepartment of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah cDepartment of Psychology, The University of Albany, Albany, New York dDepartment of Chemistry, Institute for Arctic Biology and the IDeA Network for Biomedical Research Excellence, The University of Alaska, Fairbanks, Alaska, USA.
Abstract:
Chronic stress can influence behaviors associated with medial prefrontal cortex (mPFC) function, such as cognition and emotion regulation. Dopamine in the mPFC is responsive to stress and modulates its behavioral effects. The current study tested whether exposure to 10 days of chronic unpredictable stress (CUS) altered the effects of acute elevation stress on dopamine release in the mPFC and on spatial recognition memory. Male rats previously exposed to CUS or nonstressed controls were tested behaviorally, underwent microdialysis to assess mPFC dopamine levels or underwent blood sampling for corticosterone analysis. Dopamine in the mPFC significantly increased in both groups during acute elevation stress compared with baseline levels, but the level was attenuated in CUS rats compared with controls. Control rats exposed to elevation stress immediately before the T-maze test showed impaired performance, whereas CUS rats did not. No group differences were observed in general motor activity or plasma corticosterone levels following elevation stress. The present results indicate that prior exposure to this CUS procedure reduced dopamine release in the mPFC during acute elevation stress and prevented the impairment of performance on a spatial recognition test following an acute stressor. These findings may contribute to an understanding of the complex behavioral consequences of stress.
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