Benzodiazepine-receptor mediated inhibition of isolation-induced aggression in mice

The effects of a benzodiazepine receptor agonist (diazepam), antagonist (Ro 15-1788), and an "active" antagonist [inverse agonist] (3-carboethoxy-beta-carboline) were examined in an isolation-induced model of aggression. Diazepam (4 mg/kg) and 3-carboethoxy-beta-carboline (10 mg/kg), but not Ro 15-1788, significantly inhibited aggressive behavior in this model. Ro 15-1788 (10 mg/kg) reduced the anti-aggressive actions of both diazepam and 3-carboethoxy-beta-carboline, while mice treated with a combination of diazepam and 3-carboethoxy-beta-carboline had aggression scores increased to values not significantly different from vehicle treated mice. These findings suggest that both diazepam and 3-carboethoxy-beta-carboline have anti-aggressive properties in the isolation-induced model of aggression which are mediated through CNS benzodiazepine receptors.