EFFECTS OF HA-966 ON CONFLICT, SOCIAL-INTERACTION, AND PLUS MAZE BEHAVIORS

Antagonists at the N-methyl-D-aspartate (NMDA) receptor share a number of properties, including anticonvulsant and anxiolytic-like behaviors. In the Cook and Davidson conditioned conflict paradigm, the NMDA receptor complex antagonists HA-966 (1 and 3 mg/kg), CPP (10 mg/kg), MK-801 (0.03 mg/kg), and the benzodiazepine, diazepam (3 and 10 mg/kg) significantly disinhibited conflict responding. Likewise, in the social interaction test and elevated plus maze assay, two non-conditioned paradigms predictive of anxiolytic activity, the NMDA antagonists HA-966, CPP, and MK-801, as well as diazepam, all significantly increased both social interaction time and open arm exploration time, respectively. In general, antagonism of the NMDA receptor complex results in anxiolytic behavior in rodents. Moreover, selective antagonism at the strychnine-insensitive glycine modulatory site (HA-966) may represent a new and novel class of compounds with potential therapeutic efficacy in anxiety.