NMDA receptor blockade specifically impedes the acquisition of incentive salience attribution

Glutamatergic signaling plays an important role in learning and memory. Using Pavlovian conditioned approach procedures, the mechanisms that drive stimulus-reward learning and memory have been investigated. However, there are instances where reward-predictive stimuli can function beyond being solely predictive and can be attributed with “motivational value” or incentive salience. Using a Pavlovian conditioned approach procedure consisting of two different but equally predictive stimuli (lever vs. tone) we investigated the role NMDA receptor function has in the attribution of incentive salience. The results revealed that the administration of MK-801, an NMDA receptor antagonist, during acquisition of Pavlovian conditioned approach promoted goal-tracking to a lever stimulus, while control animals learned to sign-track. Moreover, within the same animals, the use of a tone stimulus elicited goal-tracking responses that were unaffected by MK-801 pretreatments. Furthermore, a lever CS that elicited sign-tracking served as a more robust conditioned reinforcer than a tone CS that elicited goal-tracking or a lever CS that elicited goal-tracking via MK-801 pretreatments. Collectively, these results demonstrate that NMDA receptor antagonism can alter the stimulus-reward relationship learned and prevent the attribution of incentive salience, rather than impede general learning.