Blockade of NMDA receptors in prelimbic cortex induces an enduring amnesia for odor-reward associative learning

Abstract

The competitive antagonist 2-amino-5-phosphonoeptanoic acid (APV) was injected intracerebroventricularly to determine the involvement of NMDA receptors in different stages of memory consolidation. Subsequent experiments used local injections to determine possible sites of drug action. Rats were trained in a rapidly learned olfactory task to find palatable food in a hole in a sponge impregnated with the target odor in the presence of two other sponges with nonrewarded odors. APV injections were made intracerebroventricularly 5 min or 2 hr after the end of the training, and a retention test was given 48 hr later. The results showed that blockade of NMDA receptors immediately after training induces a profound and enduring amnesia with no effect when the treatment is delayed at 2 hr after training. To address the question of the effective sites of action of the intracerebroventricular treatment, APV injections into the hippocampus and into the prelimblic region of the frontal cortex (PLC) were made. Blockade of NMDA receptors into the PLC but not into the hippocampus impaired memory formation of the odor-reward association. The amnesia is not transient, because the retention tests were made 48 hr after training. These results underlie the role of NMDA receptors in the early stage of consolidation of a simple odor-reward associative memory and confirm the role of the PLC in the consolidation of long-term memory.

Figure 1.

Intracerebroventricular injections of APV. Latency to make the correct response over the last training trial, the retention, and the relearning. Independent groups were treated 5 min or 2 hr after training with APV or vehicle solution. The retention test was made 48 hr later. The APV 5 min group is significantly different from the vehicle 5 min group (✳p < 0.01) and the APV 2 hr group ( p < 0.01). Significant differences were observed between the last trial of training and the retention test for the APV 5 min group (✻p < 0.01) and between the retention test and the relearning (★p < 0.01). Together, these data indicate that blockade of NMDA receptors immediately after training (1) induces amnesia with no effect when the treatment is 2 hr after training and (2) does not block the relearning.

Figure 2.

Position of the cannulas and injection site. Top, Cannulas in the PLC (field CA1). Bottom, Cannulas in the hippocampus.

Figure 3.

APV injections into the hippocampus. Latency to make the correct response over the last training trial, the retention, and the relearning.Groups were treated 5 min after training with APV or vehicle solution. The retention test was made 48 hr later. No difference was observed between groups and between the last learning trial, the retention test, and the relearning.These data indicate that blockade of NMDA receptors into the hippocampus does not impair the memory formation of the odor–reward association.

Figure 4.

APV injections into the prelimbic cortex. Latency to make the correct response over the last training trial, the retention, and the relearning. Groups were treated 5 min after training with APV or vehicle solution. The retention test was made 48 hr later. The APV group is significantly different from the vehicle group at the retention test ( p < 0.01). Significant differences were observed between the retention test and the last learning trial (✻p < 0.01) and between the retention test and the relearning (★p < 0.01) for the APV group. These data suggest that blockade of NMDA receptors into the prelimbic cortex after the training induces amnesia but does not block the relearning.