The effects of NMDA antagonists on punished exploration in mice

Abstract

Previous studies have reported that several NMDA antagonists show anxiolytic-like activity in behavioural tests. To follow up the observation that AP7 increased the punished exploration of mice in the four plate test, several NMDA antagonists were tested in this procedure in shocked and non-shocked conditions. AP7 increased shocked exploration without increasing non-shocked exploration. However, another competitive NMDA antagonist, CGS 19755, produced no increases in exploration in either condition. The non-competitive antagonists, phencyclidine, MK-801 and dextromethorphan, produced dose-related increases in activity in both the non-shocked and shocked conditions. This effect is probably best considered a psychomotor stimulant action rather than an anxiolytic-like activity. The non-competitive NMDA antagonist, SL 82.0715, which acts at the polyamine site, and the ethyl ester of 7-chlorokynurenic acid, which acts at the glycine modulatory site, produced only decreases in exploration indicating that they lack both stimulant and anxiolytic activity. Although providing little evidence for anxiolytic action the present results further demonstrate that compounds acting at different sites within the NMDA receptor complex can give rise to very different pharmacological and behavioural effects.