Mesocorticolimbic dopamine pathways in the reinforcement of social hierarchy

초록

Social animals engage in competition for limited resources, leading to the establishment of hierarchical structures. While previous research has highlighted the role of brain regions such as the medial prefrontal cortex (mPFC) in regulating social competition and hierarchy, the mechanisms through which repeated social competition shapes and maintains these hierarchies remain incompletely understood. We propose that the mesocorticolimbic dopamine pathway, known for its involvement in reward processing, motivation, and reinforcement learning, plays a critical role in reinforcing social hierarchy through repeated social competition. To test this hypothesis, we employed conditioned place preference and aversion paradigms based on experiences of social wins or losses in mice. Our findings indicate that repeated experiences of social winning and losing exert opposing effects on the reinforcement of social hierarchy. Notably, dominant individuals exhibited a preference for engaging in social competition, whereas subordinate individuals tended to avoid it. Investigating the role of the ventral tegmental area (VTA), we found that inhibition of dopaminergic neurons in the VTA (VTADA) reduced social hierarchy, whereas inhibition of GABAergic neurons in the VTA (VTAGABA) enhanced it. Furthermore, selective inhibition of VTADA neurons projecting to the nucleus accumbens (VTADA-NAc) resulted in a diminished social hierarchy, while inhibition of VTADA neurons projecting to the mPFC (VTADA-mPFC) led to an increase in hierarchical ranking. These results suggest that social hierarchy is differentially regulated by distinct VTA neuronal subtypes and their specific projections, providing novel insights into the neuronal mechanisms underlying social dominance and competition.