Effects of NMDA receptor blockade on behaviors differentially affected by fimbria/fornix and amygdala lesions

Abstract

We studied the effects of MK-801, a noncompetitive NMDA receptor antagonist, on acquisition and expression of the food conditioned cue preference (CCP) in the eight-arm radial maze. In this task, food-deprived rats are confined on alternate days in one arm of a radial maze with food and in another arm with no food. After several such training trials, they are given a choice between the two arms, both of which are empty. Normal rats spend more time in the arm that formerly contained food. We previously showed that this CCP is eliminated by lesions of the lateral nucleus of the amygdala. A single 10-min session of preexposure to the maze with no food retards acquisition of the CCP. This retardation is eliminated by fornix lesions, suggesting that hippocampus-based learning about the environment during the preexposure session suppresses subsequent amygdala-based CCP learning. In the present experiment, rats that received MK-801 before a preexposure session exhibited CCPs comparable to those for animals that had not experienced preexposure. We attribute this effect to the prevention of hippocampus-based learning during the preexposure due to NMDA receptor blockade. In other groups of rats, MK-801 given before the training trials or before the test trial eliminated the CCP in rats that had not received preexposure to the maze. The prevention of both acquisition and expression of the amygdala-based food CCP by MK-801 may distinguish the memory-related function of NMDA receptors in the amygdala from that of similar receptors in the hippocampus.