Effects of 5,7 dichlorokynurenic acid on conflict, social interaction and plus maze behaviors.
Antagonists at the N-methyl-D-aspartate (NMDA) receptor site share a number of properties including anticonvulsant and anxiolytic-like behaviors. In the social interaction and elevated plus maze assay, two non-conditioned paradigms predictive of anxiolytic activity, the NMDA antagonists 5,7 DCKA, CPP and MK-801, as well as diazepam, all significantly increased both social interaction time and open arm exploration time, respectively. Likewise, in the Cook and Davidson conditioned conflict paradigm, the NMDA antagonists 5,7 dichlorokynurenic acid (DCKA; 100 and 173 mg/kg), (+-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 10 mg/kg), dizolcipine (MK-801; 0.03 mg/kg) and the benzodiazepine, 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 discrimination paradigm. In general, antagonism at the NMDA receptor complex results in anxiolytic-like behavior in rodents. In particular, selective antagonism at the strychnine-insensitive glycine modulatory site (5,7 DCKA) may represent a new and novel class of compounds with potential therapeutic efficacy in anxiety without some of the side effects associated with other NMDA antagonists.
Corbett
R
R
Department of Biological Research, Hoechst-Roussel Pharmaceuticals, Somerville, NJ 08876.
Dunn
R W
RW
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D003220:Conflict, Psychological; D003975:Diazepam / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005998:Glycine / Q000037:antagonists & inhibitors; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012919:Social Behavior
D014151:Anti-Anxiety Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D007736:Kynurenic Acid; D003975:Diazepam; C066192:5,7-dichlorokynurenic acid; D005998:Glycine