Aggression modulator: Understanding the multifaceted role of the dorsal raphe nucleus

Aggressive behavior is instinctively driven behavior that helps animals to survive and reproduce and is closely related to multiple behavioral and physiological processes. The dorsal raphe nucleus (DRN) is an evolutionarily conserved midbrain structure that regulates aggressive behavior by integrating diverse brain inputs. The DRN consists predominantly of serotonergic (5-HT:5-hydroxytryptamine) neurons and decreased 5-HT activity was classically thought to increase aggression. However, recent studies challenge this 5-HT deficiency model, revealing a more complex role for the DRN 5-HT system in aggression. Furthermore, emerging evidence has shown that non-5-HT populations in the DRN and specific neural circuits contribute to the escalation of aggressive behavior. This review argues that the DRN serves as a multifaceted modulator of aggression, acting not only via 5-HT but also via other neurotransmitters and neural pathways, as well as different subsets of 5-HT neurons. In addition, we discuss the contribution of DRN neurons in the behavioral and physiological aspects implicated in aggressive behavior, such as arousal, reward, and impulsivity, to further our understanding of DRN-mediated aggression modulation.