Intra-cerebellar infusion of NMDA receptor antagonist AP5 disrupts classical eyeblink conditioning in rabbits

Rabbits were infused with AP5, an NMDA receptor antagonist, into the region of the cerebellar interpositus nucleus during classical eyeblink conditioning with a tone conditioned stimulus and an air puff unconditioned stimulus. Acquisition of the conditioned eyeblink response was delayed in rabbits infused with AP5 but the NMDA receptor antagonist had little effect on conditioned responses when these same rabbits were infused a second time after reaching asymptotic responding levels. Some rabbits that received AP5 infusions for the first time after the conditioned response was well learned showed temporary alterations in response timing. These data indicate that NMDA receptor activity is involved in the acquisition of classically conditioned eyeblink response and may also be involved in regulating cellular processes involved in response timing and other aspects of conditioned response execution.