EFFECTS OF 5,7DICHLOROKYNURENIC ACID ON CONFLICT, SOCIAL-INTERACTION AND PLUS-MAZE BEHAVIORS

Antagonists at the N-methyl-D-aspartate (NMDA) receptor site share a n umber of properties including anticonvulsant and anxiolytic-like behav iors. In the social interaction and elevated plus maze assay, two non- conditioned paradigms predictive of anxiolytic activity, the NMDA anta gonists 5,7 DCKA, CPP and MK-801, as well as diazepam, all significant ly increased both social interaction time and open arm exploration tim e, respectively. Likewise, in the Cook and Davidson conditioned confli ct paradigm, the NMDA antagonists 5,7 dichlorokynurenic acid (DCKA; 10 0 and 173 mg/kg), ( +/- )-3-2-carboxypiperazin-4-yl)-propyl-l-phosphon ic acid (CPP; 10 mg/kg), dizolcipine (MK-801; 0.03 mg/kg) and the benz odiazepine, diazepam (3-30 mg/kg) significantly disinhibited conflict responding. In addition, administration of 5,7 DCKA did not result in a generalization to a MK-801 discriminative cue in a drug discriminati on paradigm. In general, antagonism at the NMDA receptor complex resul ts in anxiolytic-like behavior in rodents. In particular, selective an tagonism at the strychnine-insensitive glycine modulatory site (5,7 DC KA) may represent a new and novel class of compounds with potential th erapeutic efficacy in anxiety without some of the side effects associa ted with other NMDA antagonists.