NMDA antagonists disrupt timing behaviour in rats

The behavioural effects of six compounds with N-methyl-D-aspartate (NMDA) antagonist properties were compared on the responding of rats maintained by a differential reinforcement of low rate 15s (DRL-15s) schedule. This schedule requires that responses be temporally spaced in order to be reinforced (timing behaviour). The number of reinforcers obtained was decreased by the non-competitive NMDA antagonists phencyclidine, dizocilpine and memantine, by the competitive NMDA antagonist CGS 19755, by the antitussive drug dextromethorphan, but not by the polyamine site antagonist eliprodil (SL 82.0715). Small increases in response rates were produced by phencyclidine and memantine, and dizocilpine gave rise to very marked increases in rates. CGS 19755, eliprodil and dextromethorphan only decreased rates of responding at high doses. Analysis of drug action in terms of inter-response times (IRT) showed that, except for eliprodil, all compounds shifted the peaks of the IRT distributions to the left. The percentage of short IRTs (response bursts) showed statistically significant increases after administration of dizocilpine, phencyclidine, memantine and CGS 19755. These results show that timing behaviour in rats is disturbed by several NMDA antagonists, although eliprodil, while decreasing responding at high doses, did not disrupt efficient timing.