Repeated Binge-Like Alcohol Drinking Heightens Aggression in Mice

Abstract Rationale In humans, alcohol drinking is a significant driver of violent behaviors such as assaults and homicides. While acute intoxication is known to produce heightened aggression, little is known about alcohol’s long-term effects. Emerging evidence, however, suggests that chronic alcohol intake can promote heightened aggression, including during abstinence and may also sensitize individuals to alcohol’s acute aggression-heightening effects. Objectives The goal of this study was to test the effects of chronic binge-like ethanol drinking on both alcohol-involved and alcohol-uninvolved aggression in male CFW mice. We aimed to model individual differences in binge drinking and assess changes in aggression during both acute and protracted abstinence. Results After 5 weeks of Drinking in the Dark (DID), CFW mice that showed higher levels of EtOH drinking (‘high drinkers’, 1.33 g/kg/h) became more aggressive than low drinkers (0.45 g/kg/h) and H₂O controls, as measured via frequency of attack bites during resident-intruder fighting. In the first aggressive encounter following 1 week of abstinence, animals with an alcohol drinking history initiate a fight more rapidly and with greater consistency than H₂O controls. We also found that a single session of binge-like alcohol drinking acutely heightened aggression regardless of drinking history. Conclusions These results suggest that repeated binge-like alcohol drinking causes escalations in alcohol-uninvolved aggression during acute (in high drinkers) and protracted abstinence (in all alcohol drinkers). However, chronic alcohol intake does not appear to sensitize animals to alcohol-involved aggression. These findings support the utility of genetically heterogeneous CFW mice for modeling individual variability in alcohol-related aggression.