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The present study tested the effect of two non-competitive NMDA receptor antagonists, ketamine and phencyclidine, on the induction of long-term depression (LTD) in the dentate gyrus of urethane-anesthetized rats. Both drugs blocked the induction of LTD as well as long-term potentiation (LTP). NMDA receptor activation thus seems to be required for the induction of both LTD and LTP in the dentate gyrus. High-intensity conditioning stimulation did not overcome the phencyclidine block of LTD. Strong, but brief, postsynaptic depolarization is apparently not the only event needed to trigger LTD.
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