NMDA receptor activation antagonizes the NMDA antagonist-induced antianxiety effect in the elevated plus-maze test in mice.

BACKGROUND The purpose of this study was to determine how the activation of different regulatory domains of the NMDA complex affects the antianxiety effect of antagonists acting at its distinct binding sites. METHODS The anxiolytic-like activity was assessed by the elevated plus-maze test in mice. RESULTS The anxiolytic activity of CGP 37849 (a competitive NMDA receptor antagonist) and L-701,324 (an antagonist at glycine site) was confirmed, but effects of both were significantly reduced by N-methyl-D-aspartic acid (NMDA) or by D-serine agonists at glutamate and glycine site of the NMDA receptor complex, respectively. CONCLUSION The obtained data suggest that stimulation of the glutamate or glycine recognition site of the NMDA receptor complex significantly decreases the antianxiety properties of antagonists of either site.