Dopamine D2 receptor within the intermediate region of the lateral septum modulate social hierarchy in male mice

The dopamine (DA) system has long been involved in social hierarchies; however, the specific mechanisms have not been elucidated. The lateral septum (LS) is a limbic brain structure that regulates various emotional, motivational, and social behaviors. DA receptors are abundantly expressed in the LS, modulating its functions. In this study, we evaluated the functions of DA receptors within different subregions of the LS in social dominance using a confrontation tube test in male mice. The results showed that mice living in social groups formed linear dominance hierarchies after a few days of cohousing, and the subordinates showed increased anxiety. Fos expressions was elevated in the entire LS after a confrontation tube test in the subordinates. However, DA neurons were more activated in the dominates within the ventral tegmental area and the dorsal raphe nucleus. Quantitative real-time polymerase chain reaction results showed that D2 receptor (D2R) within the intermediate region of the LS (LSi) were elevated in the subordinate. In the following pharmacological studies, we found simultaneous D2R activation in the dominants and D2R inhibition in the subordinates switched the original dominant-subordinate relationship. The aforementioned results suggested that D2R within the LSi plays an important role in social dominance in male mice. These findings improve our understanding of the neural mechanisms underlying the social hierarchy, which is closely related to our social life and happiness.