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<p>Alcohol is known to alter social behavior, yet how it acts on the brain to produce specific, rank-dependent changes in social competition remains unknown. Here we show in male mice that a low dose of alcohol induces a rapid, transient, and highly selective upward shift in social hierarchy: it promotes dominance behavior exclusively in mid-ranking animals, enabling them to stably outcompete their immediate superior. Critically, this effect was absent in both dominant and the lowest-ranking subordinates, demonstrating a precise social-context gating of alcohol’s action. This rank-specific effect is also absent in females. Using cFos mapping and chemogenetic manipulations, we identify CaMKIIα-expressing glutamatergic neurons in the prelimbic prefrontal cortex (PL) as both necessary and sufficient for this alcohol-driven social ascent. Anatomical and functional analyses reveal that alcohol selectively recruits the PL→nucleus accumbens (NAc) pathway, and projection-specific inhibition of this circuit abolishes the behavioral effect. These findings delineate a social rank–gated prefrontal–accumbal circuit that mediates the selective pro-dominance action of alcohol, providing a mechanistic basis for how a globally acting drug can produce precise, context-dependent changes in social structure.</p>

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Acute alcohol triggers rank-specific social ascent through a prefrontal-accumbens circuit in male mice

  • 期刊论文

  • 发表日期：

    2026年7月16日

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  • Xiao Jia,
  • Hui Zhou,
  • Can Tang,
  • Jiale Ye,
  • Zhiyang Yu,
  • Jun-Li Cao,
  • Can Li,
  • Kunwei Wu

摘要

Alcohol is known to alter social behavior, yet how it acts on the brain to produce specific, rank-dependent changes in social competition remains unknown. Here we show in male mice that a low dose of alcohol induces a rapid, transient, and highly selective upward shift in social hierarchy: it promotes dominance behavior exclusively in mid-ranking animals, enabling them to stably outcompete their immediate superior. Critically, this effect was absent in both dominant and the lowest-ranking subordinates, demonstrating a precise social-context gating of alcohol’s action. This rank-specific effect is also absent in females. Using cFos mapping and chemogenetic manipulations, we identify CaMKIIα-expressing glutamatergic neurons in the prelimbic prefrontal cortex (PL) as both necessary and sufficient for this alcohol-driven social ascent. Anatomical and functional analyses reveal that alcohol selectively recruits the PL→nucleus accumbens (NAc) pathway, and projection-specific inhibition of this circuit abolishes the behavioral effect. These findings delineate a social rank–gated prefrontal–accumbal circuit that mediates the selective pro-dominance action of alcohol, providing a mechanistic basis for how a globally acting drug can produce precise, context-dependent changes in social structure.