Rodent models of aggression: from mechanisms to clinical translation.

Aggression is an evolutionarily conserved social behavior that becomes clinically relevant when it loses contextual and inhibitory regulation. Rodent models do not serve to reproduce the full complexity of human violence, with its legal, moral, cultural, and interpersonal dimensions. Their translational value lies instead in making core mechanisms of aggression regulation experimentally accessible. This article discusses how rodent models help to distinguish adaptive from dysregulated aggression; to select clinically informative paradigms; and to identify causal pathways that shape attack threshold, escalation, persistence, reward value, and inhibitory control. Rodent studies have mapped a multilevel control architecture in which social sensory threat is appraised through amygdala-hypothalamic pathways, hypothalamic and midbrain circuits organize attack-related behavior, and corticostriatal systems contribute to motivation and regulatory control. Rather than acting as fixed modules, these circuits are shaped by experience, internal state, sex and endocrine modulation, immune signaling, and aggression-related reward. Next-generation models should therefore complement traditional reductionist assays with longitudinal trajectories, socially embedded phenotyping, dysregulation readouts, and measures of distributed network and body-brain states. Within TRR 379, rodent models enable mechanism-focused translation by helping to identify biosignatures and modifiable pathways for future interventions in dysregulated aggression.