Excessive aggression as model of violence: a critical evaluation of current preclinical methods.

RATIONALE: Preclinical experimental models of pathological aggressive behavior are a sorely understudied and difficult research area.
OBJECTIVES: How valid, reliable, productive, and informative are the most frequently used animal models of excessive aggressive behavior?
METHODS: The rationale, key methodological features, supporting data, and arguments as well as their disadvantages and limitations of the most frequently used animal models for excessive aggressive behavior are summarized and their validity and reliability are evaluated.
RESULTS: Excessive aggressive behavior is validly and reliably seen in (1) a proportion of feral-derived rats and selectively bred mice; (2) rats with compromised adrenal function resulting in a hypoglucocorticoid state; (3) a significant minority of mice, rats, and monkeys after consumption of a moderate dose of alcohol; and (4) resident animals of various species after social instigation. Limitations of these procedures include restrictive animal research regulations, the requirement of expertise in surgical, pharmacological, and behavioral techniques, and the behaviorally impoverished mouse strains that are used in molecular genetics research. Promising recent initiatives for novel experimental models include aggressive behaviors that are evoked by optogenetic stimulation and induced by the manipulation of early social experiences such as isolation rearing or social stress.
CONCLUSIONS: One of the most significant challenges for animal models of excessive, potentially abnormal aggressive behavior is the characterization of distinctive neurobiological mechanisms that differ from those governing species-typical aggressive behavior. Identifying novel targets for effective intervention requires increased understanding of the distinctive molecular, cellular, and circuit mechanisms for each type of abnormal aggressive behavior.