Effects of ketamine and 1-glutamic acid diethyl ester on concept learning in rats.

The effects of ketamine, an NMDA receptor antagonist, and 1-glutamic acid diethyl ester (LGDE), a non-NMDA glutamate antagonist, were evaluated in the acquisition of concept learning in a water maze. In concept learning, the rats must locate an invisible platform whose location changes from day to day. In spatial learning (Morris task), the rats must locate an invisible (or visible) platform whose location does not change. Ketamine increased quadrant entries at 5, 10 and 20 mg/kg, and latencies at 10 and 20 mg/kg on the final two days of training on the concept task. At 5 mg/kg ketamine disrupted concept learning but not spatial learning or visuo-motor coordination as assessed by invisible and visible platform conditions of the Morris maze. Progressively higher doses of ketamine affected first the invisible condition and then the visible platform condition. On the other hand, LGDE did not affect the Morris task at any dose. However, there was no decrease in latencies over days in concept learning at the two highest doses (240 and 360 mg/kg) of LGDE. Thus LGDE appeared to slow down decision time in the concept task but not the spatial task in the absence of an effect on quadrant entries in any version. These results indicate that NMDA receptors are involved in spatial and concept learning. Non-NMDA receptors appear to be involved only in concept learning.