PREVENTION OF THE PRO-AGGRESSIVE EFFECTS OF ALCOHOL IN RATS AND SQUIRREL-MONKEYS BY BENZODIAZEPINE RECEPTOR ANTAGONISTS

Pharmacological manipulations at the benzodiazepine-GABA(A)-chloride i onophore receptor complex modify some of the behavioral and physiologi cal actions of alcohol (ethanol). The interactions between alcohol, be nzodiazepines and aggression were examined in similar ethopharmacologi cal studies in squirrel monkeys and in rats in confrontations with con specifics. Dominant male squirrel monkeys were tested (1) within their social groups, and (2) in dyadic confrontations with ''rival'' males from a different social group, and resident male rats were tested in t heir home cage in confrontations with an inexperienced male intruder. Low doses of alcohol (0.1-0.3 g/kg) increased aggressive behaviors in dominant squirrel monkeys and a subgroup of resident rats, whereas hig h doses of alcohol (1-3 g/kg) decreased aggression and produced marked motor incoordination. Individuals that showed alcohol-enhanced aggres sion were selected, and pretreated with benzodiazepine antagonists (fl umazenil, ZK 93426) prior to alcohol administration. Both ZK 93426 (3 mg/kg) and flumazenil (10 mg/kg) blocked the aggression-enhancing effe cts of alcohol in dominant squirrel monkeys and resident rats in confr ontations with conspecifics. Neither compound altered the reductions i n aggression and increases in inactivity produced by high doses of alc ohol. Interestingly, agonist-like increased feeding and inverse agonis t-like reductions in social behaviors were observed simultaneously at the same dose of flumazenil, in the same individual and testing situat ion. ZK 93426 did not alter feeding but also reduced social behaviors. The two antagonists were also not equipotent in their interactions wi th alcohol. ZK 93426 reduced alcohol-induced motor incoordination in s quirrel monkeys, whereas flumazenil did not. In fact, flumazenil poten tiated the effects of low doses of alcohol. Locomotion was reduced, wh ile staggering and time spent sitting were increased in squirrel monke ys pretreated with flumazenil plus low to moderate alcohol doses that previously did not produce these effects when administered alone. The blockade of the motor-incoordinating effects of alcohol may depend on inverse agonist activities of the antagonist acting at the GABA(A)-ben zodiazepine receptor coupled chloride channel.