MK801 RETARDS ACQUISITION OF A CLASSICALLY-CONDITIONED RESPONSE WITHOUT AFFECTING CONDITIONING-RELATED ALTERATIONS IN PERFORANT PATH-GRANULE CELL SYNAPTIC TRANSMISSION

The contributions of N-methyl-D-aspartate (NMDA) receptor activity to classical conditioning of the rabbit nictitating membrane (NM) respons e and conditioning-related alterations of the hippocampal perforant pa th-granule cell response were examined. Subcutaneous injections of the noncompetitive 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-d ependent 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 potentiatio n of perforant path-granule cell responses. The within-trial decrease in spike amplitude, relative to the between-trial response, was also n ot affected by MK801 administration. These results suggest that NMDA-m ediated activity contributes to classical conditioning of the rabbit N M response and raise the possibility that conditioning-related alterat ions of perforant path-granule cell synaptic transmission are not NMDA dependent.