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Updated: Nov 4, 2025

The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice
Published on: October 24, 2018
Epicatechin treatment generates resilience to chronic mild stress-induced depression in a murine model
Mirna Guadalupe Martínez-Damas1, Alma Delia Genis-Mendoza2, Verónica Pérez-de la Cruz3
1Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, México; Subdirección de Enseñanza e Investigación, Centro Médico Nacional "20 de Noviembre", Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Ciudad de México, México.
Abstract:
Several studies have proposed that cocoa products-enriched in flavonoids reduce anxiety and depressive symptoms. (-)-Epicatechin (Epi), a flavonoid present in high concentration in cocoa, has been associated with many dark chocolate effects and has been postulated as an exercise mimetic. Physical exercise is used as an adjuvant treatment for many depressive patients. This study aimed to evaluate the impact of Epi on resilience in depression-like behavior in a murine model. Male mice were randomly selected and divided into four groups (n = 8/group). Beginning at the age of 8-9 weeks, the mice were subjected to Chronic Mild Stress (CMS) and/or treatment Epi for five weeks. Epi was administered by oral gavage twice daily/5 weeks. The control group was housed in conditions without stress and Epi treatment. Depressive behavior was evaluated by sucrose preference and open field tests. Interestingly, Epi reduced anhedonia and anxiogenic behavior in the murine stress model. These results suggest that Epi induces resilience to stress-induced depression. Furthermore, our findings propose that muscles respond to Epi treatment according to their type of metabolism and that kynurenine aminotransferases (KATs) could play a role in modulating this response.

