Cell-Type-Specific Role of {Delta}FosB in Nucleus Accumbens In Modulating Intermale Aggression

A growing number of studies implicate the brain's reward circuitry in aggressive behavior. However, the cellular and molecular mechanisms within brain reward regions that modulate the intensity of aggression as well as motivation for it have been underexplored. Here, we investigate the cell-type-specific influence of FosB, a transcription factor known to regulate a range of reward and motivated behaviors, acting in the nucleus accumbens (NAc), a key reward region, in male aggression in mice. We show that FosB is specifically increased in dopamine D1 receptor (Drd1)-expressing medium spiny neurons (D1-MSNs) in NAc after repeated aggressive encounters. Viral-mediated induction of FosB selectively in D1-MSNs of NAc intensifies aggressive behavior without affecting the preference for the aggression-paired context in a conditioned place preference (CPP) assay. In contrast, FosB induction selectively in D2-MSNs reduces the time spent exploring the aggression-paired context during CPP without affecting the intensity of aggression per se. These data strongly support a dissociable cell-type-specific role for FosB in the NAc in modulating aggression and aggression reward.

SIGNIFICANCE STATEMENT Aggressive behavior is associated with several neuropsychiatric disorders and can be disruptive for affected individuals as well as their victims. Studies have shown a positive reinforcement mechanism underlying aggressive behavior that shares many common features with drug addiction. Here, we explore the cell-type-specific role of the addiction-associated transcription factor FosB in the nucleus accumbens in aggression. We found that FosB expression promotes aggressive behavior, effects that are dissociable from its effects on aggression reward. This finding is a significant first step in identifying therapeutic targets for the reduction of aggressive behavior across a range of neuropsychiatric illnesses.