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

Abstract

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.

An emerging role for the lateral habenula in aggressive behavior

“…Classically, RI consists of placing an intruder male conspecific in the home cage of the resident animal and observing subsequent aggressive behavior. This paradigm has been extensively used in species from fish to flies to rodents (Miczek et al 2013). When RI is repeated over multiple days, the probability of winning a fight increases with each successive victory (Oyegbile and Marler 2005, Schwartzer et al 2013).…”

Neural and Behavioral Correlates of Alcohol-Induced Aggression Under Provocation

“…So far, the neural underpinnings of alcohol-induced aggression have mainly been studied in animal models of excessive aggression (eg, resident-intruder paradigms), which might not be representative for humans (Miczek et al, 2013). To the best of our knowledge, the present study investigates for the first time the neural mechanisms of alcohol-induced human aggression in relation to provocation at moderate alcohol intoxication (breath alcohol concentration (BrAC) = 0.6 g/kg).…”

Neural mechanisms of predatory aggression in rats—Implications for abnormal intraspecific aggression

“…We recently developed two laboratory models that mimic important characteristics of affective/reactive and instrumental/proactive forms of aggression, and proposed behavioral methods to differentiate species-typical and abnormal forms of aggression [17][18][19][20]. Importantly for the present study, we found that rats submitted to one of these models -the glucocorticoid dysfunction model of abnormal aggression-deliver bites to vulnerable body parts of conspecifics (head, throat and belly), which is accompanied by low intention signaling by threats, disturbed social behavior, and reduced autonomic arousal, features that are in many respects to similar to the symptoms of aggressive antisocial personality disordered subjects [17][18][19][20]. We found that in this model, aggressive encounters increase the activation of the lateral hypothalamus, central amygdala and ventral periaqueductal grey (PAG) above the levels seen in controls submitted to fights (i.e.…”