Escalated aggression in animal models: shedding new light on mesocorticolimbic circuits

• Violent and callous acts in humans are validly modeled in animals.
• These models comprise selective breeding, low glucocorticoids, and alcohol.
• Optogenetic stimulation activates microcircuits of escalated aggressive behavior.
• These microcircuits encompass the VTA-mPFC and hypothalamic-limbic structures.

Recent developments promise to significantly advance the understudied behavioral and neurobiology of aggression: (1) Animal models that capture essential features of human violence and callousness have been developed. These models range from mice that have been selectively bred for short attack latencies, monogamous prairie voles, and glucocorticoid-compromised rats to rodents and non-human primates that escalate their aggression after consuming or when withdrawing from alcohol. (2) Optogenetic stimulation and viral vector-based approaches have begun to identify overlapping and distinctive neural microcircuits and intracellular molecules for adaptive vs. excessive, maladaptive aggressive behavior in several rodent models. Projections from hypothalamic and mesencephalic neurons to the medial prefrontal cortex contain microcircuits that appear pivotal for the escalation of aggression.

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