Are reactions to frustrative nonreward in other animals a model for human anger? Neurobehavioral implications and therapeutic applications.

Anger is a powerful and mostly deleterious emotion that can impair an individual's health and social relationships and that imposes considerable costs on society at large. It is a constituent of multiple psychopathologies, most notably intermittent explosive disorder. Excessive anger can drive injurious and even lethal reactive aggression. To understand its biobehavioral origins and develop appropriate therapeutic interventions, an animal model of human anger would be quite useful. The phenomena of aggression provoked by frustrative nonreward (FNR) in other animals, including species of fish, birds, and mammals, resemble those in people in whom it elicits subjectively experienced anger. The brief history presented here traces the original, overgeneralized frustration-aggression hypothesis for humans through to the discovery of operant schedule-induced attack in birds, rodents, and ourselves to the current status of FNR as a cross-species, transdiagnostic construct within the National Institute of Health Research Domain Criteria. Brain circuitry that is activated by frustration, generates felt anger and motivates reactive aggression includes discomfort reactions likely instantiated in the insula and cingulate gyrus of the salience network and reward expectancy/prediction error mediated by the ventral striatum and other structures. Caveats in establishing a paradigm for other animals that most closely matches FNR-induced anger in people include avoiding confounds with other aggression-provoking stimuli and situations, providing evidence for aggressive motivation, as well as behavior, and demonstrating activation of homologous brain structures. With appropriate regard for these caveats, developing such paradigms appears to be the best route to advancing psychopharmacological and deep brain stimulation treatments for excessive anger. (PsycInfo Database Record (c) 2023 APA, all rights reserved).