Acute sleep deprivation rank-dependently enhances offensive aggression via the PVN in male mice

Sleep loss is a well-recognized trigger of aggression and emotional dysregulation, yet it remains unclear whether its effect on aggressive behavior interacts with social hierarchy. Here, we investigated how acute sleep deprivation (ASD) modulates offensive and defensive aggression in dominant versus subordinate male mice and explored the underlying neural mechanisms. Adult ICR mice were subjected to 12-hour overnight ASD, followed by the resident-intruder test (RIT) for offensive aggression, the defensive aggression test (DAT), and the social dominance test (SDT). ASD selectively increased the total attack time in the RIT without affecting defensive aggression or altering social rank. When stratified by social rank, ASD significantly enhanced offensive aggression in dominant, but not subordinate, mice. c-Fos immunofluorescence revealed that ASD reduced neuronal activation in the medial prefrontal cortex (mPFC) while increasing it in the paraventricular nucleus (PVN). In dominant mice, ASD further increased c-Fos expression in the ventrolateral ventromedial hypothalamus (VMHvl) and PVN, with PVN activation positively correlating with attack duration. Chemogenetic inhibition of PVN neurons using hM4Di completely reversed the ASD-induced enhancement of offensive aggression. These findings demonstrate that ASD rapidly and selectively potentiates offensive aggression in dominant individuals via PVN-dependent mechanisms, revealing a critical interaction between sleep loss and social hierarchy. This study provides new insights into the neurobiological basis of sleep-related violence and suggests that targeting the PVN or sleep regulation may offer novel intervention strategies for aggression control.