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Dopamine D2 receptors in the dorsomedial prefrontal cortex modulate social hierarchy in male mice


 Social hierarchy greatly influences behavior and health. Both human and animal studies have signaled the medial prefrontal cortex (mPFC) as specifically related to social hierarchy. Dopamine D1 receptors (D1Rs) and D2 receptors (D2Rs) are abundantly expressed in the mPFC, modulating its functions. However, it is unclear how DRs-expressing neurons in the mPFC regulate social hierarchy. Here, using a confrontation tube test, we found that most adult C57BL/6J male mice could establish a linear social rank after one week of cohabitation. Lower-rank individuals showed social anxiety together with decreased serum testosterone levels. D2Rs expression were significantly down-regulated in the dorsal part of mPFC (dmPFC) in lower-rank individuals, whereas D1Rs expression showed no significant difference among the rank groups in the whole mPFC. Virus knockdown of D2Rs in the dmPFC led to mice being particularly prone to lose the contests in the confrontation tube test. Finally, simultaneous D2Rs activation in the subordinates and D2Rs inhibition in the dominants in a pair switched their dominant-subordinate relationship. The above results indicate that D2Rs in the dmPFC play an important role in social dominance. Our findings provide novel insights into the divergent functions of prefrontal D1Rs and D2Rs in social dominance, which may contribute to ameliorating social dysfunctions along with abnormal social hierarchy.