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

BackgroundThe purpose of this study was to determine how the activation of different regulatory domains of the NMDAcomplex affects the antianxiety effect of antagonists acting at its distinct binding sites.MethodsThe anxiolytic-like activity was assessed by the elevated plus-maze test in mice.ResultsThe anxiolytic activity of CGP 37849 (a competitive NMDAreceptor 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.ConclusionThe obtained data suggest that stimulation of the glutamate or glycine recognition site of the NMDAreceptor complex significantly decreases the antianxiety properties of antagonists of either site.