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38 reviewsSocial animals encounter both environmental and social stress, yet the mechanisms by which individuals with different levels oftrait anxiety cope with these stressors, as well as the neurobiological links between trait anxiety and social cognition, remainincompletely understood. Here, male mice are classified into high-trait anxiety (HTA) and low-trait anxiety (LTA) groups based ontheir anxiety responses to elevated platform exposure in the open field test. Under observational learning-based vicarious socialdefeat stress (VSDS), HTA mice exhibit less social avoidance behavior toward CD1 aggressors than LTA mice. Fiber photometryreveals that HTA mice display higher activity of ventral tegmental area (VTA) dopaminergic (VTADA) neurons during environmentalstress, while LTA mice exhibit greater VTADA neurons activity under social stress. Viral tracing identifies the connectivity of VTADA1234567890();,:neurons and anterior cingulate cortex (ACC). Optogenetic and chemogenetic manipulations demonstrate that VTA-ACCdopaminergic circuit is necessary and sufficient for VSDS-induced social avoidance behavior in HTA and LTA mice. RNA-sequencingsuggested that VTA neuroinflammatory signaling may be a key factor contributing to the difference between HTA and LTA mice.Thus, this study reveals a neural circuit mechanism for trait anxiety-related observational learning of social avoidance behavior inmale mice, and provides a molecular mechanism in shaping trait anxiety.Neuropsychopharmacology;