NMDA receptor antagonists can enhance or impair learning performance in animals.

The effects of NMDA receptor antagonism on learning and memory were investigated using competitive (DL-2-amino-7-phosphonoheptanoate, AP7) and non-competitive (MK 801) blockers in three different learning tasks. Administration (i.p.) of drugs prior to training resulted in impaired learning performance in the place-navigation and dark-avoidance paradigms, and improved performance in the step-down passive avoidance task; however, using this treatment protocol, the possibility of drug-induced non-mnemonic effects modifying learning performance could not be excluded. Drug administration immediately post-trial had no effect in the place-navigation paradigm, and improved retention performance in the dark-avoidance and step-down avoidance tasks. The similar results obtained with both types of antagonist indicate that the observed effects are indeed due to NMDA receptor blockade, and hence that such blockade modifies learning in a task-dependent manner. Exclusion of non-mnemonic effects by using the post-trial treatment regime demonstrates that NMDA antagonists facilitate learning of passive avoidance tasks.