The first indication for a significant role of GABAA receptors in alcohol-heightened aggression was the effective blockade by benzodiazepine receptor antagonists. Pretreatment with the broad-spectrum antagonists flumazenil and ZK93426 prevented alcohol-heightened aggressive behavior in nonhuman animal models (Miczek, Barros, et al 1998; Miczek, de Almeida, et al 1998; Miczek et al 2001; de Almeida et al 2004). Furthermore, benzodiazepine agonists such as chlordiazepoxide can enhance the aggression-heightening effects of alcohol (Miczek and O’Donnell 1980). Alcohol effects on aggressive behavior depend not only on the molecular characteristics of the GABAA receptor, but also on its interactions with other positive modulators. In addition to benzodiazepines, alcohol interacts with neurosteroids, possibly at similar subunits of the GABAA receptor.
