Differential Recovery Trajectories of Behavioral and Physiological Deficits Following Chronic Unpredictable Mild Stress in Mice

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Abstract

Chronic psychological stress significantly contributes to anxiety and depressive disorders, resulting in behavioral and physiological effects. The chronic unpredictable mild stress model has been extensively validated for replicating stress-related traits in mice. Nevertheless, limited information exists regarding the natural trajectory of recovery following the cessation of the stressor and whether stress-induced changes can spontaneously ameliorate over time. This study aimed to evaluate a 4-week chronic mild stress program in mice and to assess the degree of spontaneous recovery during a 2-week stress-free interval. Male BALB/c mice were divided into three groups: control, 4-week exposure, and 2 weeks post-exposure without intervention. Behavioral results were evaluated using the open field test and sucrose preference test, in conjunction with physical assessments, including defecation frequency and coat condition score. Mice exposed to CUMS exhibited anxiety-like behaviors, characterized by diminished mobility, a preference for peripheral zones, and an increased defecation frequency, alongside physiological decline, manifesting as inadequate grooming and decreased sucrose desire (anhedonia). Following two weeks without stress exposure, only a partial recovery was noted: entry into the central zone improved; however, overall distance traveled, duration spent in the central zone, coat condition, and sucrose preference remained markedly diminished compared to controls. In conclusion, chronic stress causes enduring behavioral and physiological deficits that are not entirely reversible in a brief recovery timeframe. These findings highlight the persistent nature of stress-induced dysfunctions and illustrate the necessity of long-term measures for facilitating recovery from chronic psychological stress.
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Data may be preliminary. 18 October 2025 V1 Latest version Share on Differential Recovery Trajectories of Behavioral and Physiological Deficits Following Chronic Unpredictable Mild Stress in Mice Authors : Dicky Irnandi , Evalina Rochmah , Daniel Chandra , Nurdiana Nurdiana , Margarita Maramis , and Reny I'tishom 0000-0002-9971-7786 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.176081239.98933124/v1 155 views 81 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Chronic psychological stress significantly contributes to anxiety and depressive disorders, resulting in behavioral and physiological effects. The chronic unpredictable mild stress model has been extensively validated for replicating stress-related traits in mice. Nevertheless, limited information exists regarding the natural trajectory of recovery following the cessation of the stressor and whether stress-induced changes can spontaneously ameliorate over time. This study aimed to evaluate a 4-week chronic mild stress program in mice and to assess the degree of spontaneous recovery during a 2-week stress-free interval. Male BALB/c mice were divided into three groups: control, 4-week exposure, and 2 weeks post-exposure without intervention. Behavioral results were evaluated using the open field test and sucrose preference test, in conjunction with physical assessments, including defecation frequency and coat condition score. Mice exposed to CUMS exhibited anxiety-like behaviors, characterized by diminished mobility, a preference for peripheral zones, and an increased defecation frequency, alongside physiological decline, manifesting as inadequate grooming and decreased sucrose desire (anhedonia). Following two weeks without stress exposure, only a partial recovery was noted: entry into the central zone improved; however, overall distance traveled, duration spent in the central zone, coat condition, and sucrose preference remained markedly diminished compared to controls. In conclusion, chronic stress causes enduring behavioral and physiological deficits that are not entirely reversible in a brief recovery timeframe. These findings highlight the persistent nature of stress-induced dysfunctions and illustrate the necessity of long-term measures for facilitating recovery from chronic psychological stress. Supplementary Material File (manuscript.docx) Download 43.03 KB Information & Authors Information Version history V1 Version 1 18 October 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords anxiety-like behavior behavioral recovery chronic unpredictable mild stress psychiatric modeling stress resilience Authors Affiliations Dicky Irnandi Airlangga University Faculty of Medicine View all articles by this author Evalina Rochmah Brawijaya University Faculty of Medicine View all articles by this author Daniel Chandra Brawijaya University Faculty of Medicine View all articles by this author Nurdiana Nurdiana Brawijaya University Faculty of Medicine View all articles by this author Margarita Maramis Dr Soetomo Regional General Hospital View all articles by this author Reny I'tishom 0000-0002-9971-7786 [email protected] Airlangga University Faculty of Medicine View all articles by this author Metrics & Citations Metrics Article Usage 155 views 81 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Dicky Irnandi, Evalina Rochmah, Daniel Chandra, et al. Differential Recovery Trajectories of Behavioral and Physiological Deficits Following Chronic Unpredictable Mild Stress in Mice. Authorea . 18 October 2025. DOI: https://doi.org/10.22541/au.176081239.98933124/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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