Ethological analysis of the effects of MK-801 upon aggressive male mice: similarity to chlordiazepoxide.

Previous studies have demonstrated benzodiazepine-like effects of competitive and noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) type of excitatory amino acid receptor. The present experiment compared the effects of the benzodiazepine chlordiazepoxide and the NMDA noncompetitive antagonist MK-801 upon the behavior of aggressive male mice in dyadic interactions using ethological analysis. OF-1 male mice housed with females were administered either chlordiazepoxide (Vehicle, 3.0, 10.0 and 30.0 mg/kg IP) or MK-801 (Vehicle, 0.1, 0.3 and 0.3 mg/kg, IP) in a randomised order thirty minutes prior to pairing with unfamiliar male opponents in an unfamiliar environment. It was found that both compounds tended to increase aggressiveness and social behavior and reduce ambivalent activity consistent with approach-avoidance conflict. The increases in aggressiveness and decreases in ambivalent activity were induced by MK-801 at doses lower than those resulting in gross motor effects. These data confirm that noncompetitive antagonists of NMDA may generate a benzodiazepine-like behavioral profile.