Effects of MK-801 on acquisition, retention, and cross-modal transfer of active avoidance behavior in rats

Three experiments were conducted to examine the effects of MK-801, a noncompetitive NMDA antagonist, on acquisition, retention, and cross-modality transfer (CMT) of learning of an active avoidance response in rats. The first showed that MK-801 (0.1 mg/kg) disrupted acquisition but not retention of avoidance responding when an auditory intensity cue signaled shock. In the second experiment, the effects of MK-801 on CMT were examined by training rats to avoid shock with a visual intensity cue in the first session, then with an auditory intensity cue in two more sessions. Different groups of rats were given MK-801 (either 0.05 or 0.1 mg/kg) prior to one of the three sessions. When MK-801 was injected before visual training, the drug blocked acquisition of the avoidance task, preventing the formation of memory usable during the transfer session. When MK-801 was given before the second (transfer) session, rats did not show evidence of transfer from the previous training with the visual cue, nor did they show evidence of new learning. In the third experiment, MK-801 had no effect on avoidance behavior when it was administered immediately after training. These data suggest that NMDA receptors are involved not only in simple discrimination learning but also in neuronal processes responsible for transfer of learning between sensory modalities.