Effects of the noncompetitive NMDA receptor antagonist MK-801 on classicaleyeblink conditioning in mice

N-methyl-D-aspartate (NMDA) receptors are involved in synaptic plasticity a nd play a critical role in learning and memory. We investigated the effects of the noncompetitive NMDA receptor antagonist (+)MK-801 on classical eyeb link conditioning of mice, using various interstimulus intervals between th e conditioned stimulus (CS) and unconditioned stimulus (US). A tone was use d for the CS and a periorbital shock was used for the US. In the delay para digm, in which the US coterminated with the CS or started immediately after CS offset, the effect of (+)MK-801 (0.1 mg/kg, i.p.) was a slight impairme nt in the acquisition of the conditioned response (CR). During subsequent C S-alone trials, the responses of (+)MK-801-injected mice were extinguished as easily as those of saline-injected mice. In the trace paradigm, (+)MK-80 1 impaired acquisition of the CR with a trace interval of 250 ms more than it did with a trace interval of 100 ms, and more than in the delay paradigm . (+)MK-801 injected after acquisition of 250-ms trace conditioning did not impair expression or extinction of the CR. These results suggest that NMDA receptors are involved in acquisition of the CR during longer trace interv al conditioning more than during shorter trace interval conditioning or del ay conditioning. and that their contribution to extinction is much smaller than their contribution to acquisition in mouse eyeblink conditioning. (C) 2001 Elsevier Science Ltd. All rights reserved.