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

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.