Vicarious stress-induced emotional contagion drives sex-dependent behavioral and neurochemical alterations in mice

Vicarious stress (VS), defined as exposure to stressed peers without direct stress experience, represents a form of purely emotional stress with potential translational relevance. Here, we investigated the behavioral and neurochemical consequences of VS in male and female mice. Behavioral assessments consisted of the open field test (OFT) and elevated plus maze (EPM) for anxiety-like behavior, the Barnes maze (BM) for visuospatial learning and cognitive flexibility, and the social preference test (SPT) for social behavior. VS did not significantly alter anxiety-like measures in either sex. In contrast, learning-curves were significantly affected during BM acquisition, although this effect did not reach statistical significance in reversal learning or test phases. Social behavior was consistently disrupted in both male and female VS mice, highlighting social avoidance as a robust outcome of emotional stress. Neurochemical analyses revealed region- and sex-dependent alterations in monoaminergic systems. Serotonin concentrations increased in both brain cortex and hippocampus, while dopamine and noradrenaline concentrations showed region- and sex-dependent alterations respectively. These findings suggest that VS engages monoaminergic circuits implicated in emotion regulation, with distinct sex-specific patterns. Overall, our results demonstrate that indirect exposure to stressed peers is sufficient to modulate learning, social behavior, and monoaminergic signaling, even in the absence of direct stress experience. These findings underscore the relevance of emotional contagion in stress research and highlight the importance of controlling environmental and social factors to improve reproducibility in preclinical stress models.