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Updated: Jun 23, 2026

The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice
Published on: October 24, 2018
A novel animal paradigm of long-term, stress-induced hippocampal atrophy
Ma-Li Wong1, Claudio Mastronardi2, Julio Licinio1
1State University of New York, Upstate Medical University, Syracuse, New York 13210, USA.
Abstract:
Long-term hippocampal atrophy is a key feature of major depression. In contrast, in rodents subjected to chronic stress there is reversibly decreased hippocampal volume. We show that exposure to seven days of restraint stress alone or with antidepressant treatment combined with a persistent high-fat diet environment lasting 165 days resulted in long-term, stress-induced hippocampal volume reduction in rats, better reflecting the hippocampal shrinkage that is well documented in patients with major depressive disorder.
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