MK-801 disrupts acquisition of contextual fear conditioning but enhances memory consolidation of cued fear conditioning.

The effects of pre-training or post-training subcutaneous injections of multiple doses of the non-competitive NMDA-receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) on cued and contextual fear conditioning were examined in F344 rats. Pre-training injections of MK-801 (0.3 and 1.0 mg/kg) disrupted contextual fear conditioning but not cued fear conditioning. Post-training injections of MK-801 did not disrupt cued or contextual fear conditioning. In fact, the 0.3 mg/kg dose of MK-801 enhanced cued fear conditioning. Finally, rats were tested for MK-801-induced alterations in sensitivity to pain using the formalin test for nociception. MK-801 did not reduce sensitivity to pain. These results suggest that NMDA receptors are involved in acquisition of contextual fear conditioning but not in memory consolidation of the learned response.