Serotonergic Modulation of Social Dominance via the Dorsal Raphe–Central Amygdala Circuit in Male Mice

Social hierarchy is a fundamental aspect of social behavior in animals, influencing individual health and well-being. This study investigated the role of serotonin (5-HT) neurons in the dorsal raphe (DR) nucleus and their projections to the central amygdala (CeA) in regulating social dominance in male mice. We first observed elevated c-Fos expression in 5-HT neurons of subordinate mice, indicating heightened neuronal activity during social competition. Using chemogenetic approaches, we found that activation of DR 5-HT neurons and DR^5-HT-CeA projections significantly reduced the social rank of dominant individuals, while inhibition had negligible effects on the subordinates. Additionally, activation of the DR^5-HT-CeA circuit induced anxiety-like behaviors in dominant mice, as evidenced by reduced exploration in the open-field test. Pharmacological blockade of 5-HT1A receptors in the CeA reversed the effects of chemogenetic activation, highlighting the involvement of 5-HT1A receptors in this process. These findings underscore the critical role of the DR^5-HT-CeA circuit in modulating social dominance and suggest that 5-HT1A receptors in the CeA play a pivotal regulatory role. Overall, the current study provides new insights into the neural mechanisms underlying social hierarchy, which is closely related to our health and welfare.