Anxiolytic-like effects of N-methyl-D-aspartate-associated glycine receptor ligands in the rat potentiated startle test.

Competitive and non-competitive NMDA receptor complex antagonists have been shown to be active in various models of anxiolytic activity. This study examined the effects of ligands at the NMDA receptor-associated glycine site and two competitive NMDA receptor antagonists on the fear-potentiated startle response model for anxiolytic activity. The results show that the NMDA receptor antagonists, 2-amino-7-phosphonoheptanoate (30 mg/kg) and 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate (3 mg/kg), the glycine receptor antagonist 7-chlorokynurenate (100 mg/kg), and the glycine receptor partial agonists 3-amino-1-hydroxy-2-pyrrolidinone ((+)-HA-966) (30 mg/kg), 1-aminocyclopropane carboxylate (200-500 mg/kg) and D-cycloserine (30-300 mg/kg) blocked the potentiated startle effect. These results extend the findings of earlier studies showing anxiolytic-like effects of NMDA antagonists and glycine receptor ligands by demonstrating their effectiveness in the rat potentiated startle paradigm. These results also demonstrate the anxiolytic potential of D-cycloserine.