MK801 retards acquisition of a classically conditioned response without affecting conditioning-related alterations in perforant path-granule cell synaptic transmission

Abstract

The contributions of N-methyl-d-aspartate (NMDA) receptor activity to classical conditioning of the rabbit nictitating membrane (NM) response and conditioning-related alterations of the hippocampal perforant path-granule cell response were examined. Subcutaneous injections of the non-competitive NMDA antagonist MK801 (0.00, 0.05, or 0.10 mg/kg) were administered 75 min prior to each daily training session in a standard delay paradigm. MK801 administration resulted in a significant dose-dependent retardation in acquisition of the classically conditioned NM response. There were no consistent dose-dependent effects of MK801 on NM topography or on conditioned or unconditioned stimulus sensitivity. MK801 administration did not disrupt conditioning-related potentiation of perforant path-granule cell responses. The within-trial decrease in spike amplitude, relative to the between-trial response, was also not affected by MK801 administration. These results suggest that NMDA-mediated activity contributes to classical conditioning of the rabbit NM response and raise the possibility that conditioning-related alterations of perforant path-granule cell synaptic transmission are not NMDA dependent.