Effects of modulation of NMDA neurotransmission on response rate and duration in a conflict procedure in rats

N-Methyl-D-aspartate (NMDA) antagonists and g-aminobutyric acid agonists sh are a number of common pharmacological properties, including motor and anti convulsant effects. In the present study, site-selective NMDA antagonists w ere evaluated for potential anxiolytic efficacy and motor impairment in a m odified Geller-Seifter conflict procedure, an animal model widely used to s creen drugs for anxiolytic effects, Male Sprague-Dawley rats were trained t o respond for food reward under a multiple Fl 30 s (food only), FR 10 (food + shock) operant schedule. Consistent with the results of previous studies , the benzodiazepines chlordiazepoxide and diazepam selectively increased p unished responding and increased response durations at higher doses. The co mpetitive NMDA antagonist CGP 37,849 increased punished responding at some doses, though not selectively, and also increased response duration in both schedule components. The glycine-site modulators milacemide, ACEA 1011 and ACEA 1021, the NR2B-selective polyamine site antagonist eliprodil and NMDA did not produce anticonflict effects at any dose and had inconsistent effe cts on response durations. These results suggest that the anticonflict effe cts of NMDA antagonists are not as reliable as those of the benzodiazepines . Further research is needed to clarify the experimental conditions under w hich the anxiolytic potential of NMDA antagonists is most evident. (C) 1998 Elsevier Science Ltd. All rights reserved.