Effects of NMDA receptor channel blockade on aggression in isolated male mice

N-Methyl-D-aspartate (NMDA) receptor antagonists are perspective candidates for medication development for a number of diseases/states that are associ ated with increased aggressiveness (e.g., opioid withdrawal). The prototypi c NMDA receptor antagonist phencyclidine (PCP) itself is a widely abused su bstance and is known to elevate levels of aggression in drug users. The pre sent study was aimed at testing several drugs that share with PCP the abili ty to block NMDA receptor-associated channel. The resident-intruder procedu re was used to assess drug effects on aggressive behavior in isolated male mice. Resident aggressive mice were administered NMDA channel blockers (PCP ; 0.3-10 mg/kg), dizocilpine (MK-801; 0.01-0.3 mg/kg), memantine (1-30 mg/k g), and MRZ 2/579 (0.1-5.6 mg/kg), The competitive NMDA receptor antagonist DCPPene (0.1-5.6 mg/kg) was also tested as a compound representing an alte rnative approach to reduce activity of NMDA receptor complex. PCP, dizocilp ine, and memantine inhibited expression of aggressive behaviors only at dos es that produced ataxia. The novel channel blocker MRZ 2/579 also produced ataxia at the highest dose level but failed to affect aggressiveness. Reduc tion in aggression with a corresponding increase in sociability was observe d after administration of D-CPPene, Overall, the present results suggest th at NMDA receptor channel blockers do not exert selective effects on aggress ive behavior. (C) 1999 Wiley-Liss, Inc.