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Updated: May 13, 2026

The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice
Published on: October 24, 2018
Chronic Mild Unpredictable Stress Selectively Downregulates Exon I Bdnf mRNA in the Rat Frontal Cortex Independently
Mikhail Stepanichev1, Danil Peregud1,2, Anna Manolova1
1Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia.
Abstract:
Chronic stress is often a precursor to depression. Multiple brain mechanisms underlying the development of depression involve alterations in neurotrophin signaling. In the present study, male Wistar rats were exposed to chronic mild unpredictable stress (CMS), a well-known rodent model of depression, in order to investigate changes in BDNF content, BDNF mRNA expression, and BDNF receptor expression in different brain regions. After 8 weeks of CMS, anhedonia, a symptom of a depressive state, developed in 35% of stressed rats, while 65% remained resilient. The CMS treatment did not significantly affect the BDNF content as measured by ELISA in the frontal cortex, other neocortical regions, the hippocampus, and the medulla oblongata. The levels of exon I Bdnf mRNA decreased in the frontal cortex of both anhedonic and resilient rats. No changes were observed in exons IV, VI and IX in any of the studied brain structures, except for the hippocampus of anhedonic rats, where there was a tendency toward decreased exon IX Bdnf mRNA. The levels of Ntrk2 and Ngfr mRNAs did not significantly change in the brain after CMS. Therefore, the alterations in the expression of exon I Bdnf mRNA observed in this study were caused by chronic stress but were not associated with depression-like anhedonia.

