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.