NMDA receptor blockers prevents the facilitatory effects of post-training intra-dorsal hippocampal NMDA and physostigmine on memory retention of passive avoidance learning in rats.

In the present study, the effects of post-training intra-dorsal hippocampal (intra-CA1) injection of an N-methyl-D-aspartate (NMDA) receptor agonist and competitive or noncompetitive antagonists, on memory retention of passive avoidance learning was measured in the presence and absence of physostigmine in rats. Intra-CA1 administration of lower doses of the NMDA receptor agonist NMDA (10(-5) and 10(-4) microg/rat) did not affect memory retention, although the higher doses of the drug (10(-3), 10(-2) and 10(-1) microg/rat) increased memory retention. The greatest response was obtained with 10(-1) microg/rat of the drug. The different doses of the competitive NMDA receptor antagonist DL-AP5 (1, 3.2 and 10 microg/rat) and noncompetitive NMDA receptor antagonist MK-801 (0.5, 1 and 2 microg/rat) decreased memory retention in rats dose dependently. Both competitive and noncompetitive NMDA receptor antagonists reduced the effect of NMDA (10(-2) microg/rat). In another series of experiments, intra-CA1 injection of physostigmine (2, 3 and 4 microg/rat) improved memory retention. Post-training co-administration of lower doses of NMDA (10(-5) and 10(-4) microg/rat) and physostigmine (1 microg/rat), doses which were ineffective when given alone, significantly improved the retention latency. The competitive and noncompetitive NMDA receptor antagonists, DL-AP5 and MK-801, decreased the effect of physostigmine (2 microg/rat). Atropine decreased memory retention by itself and potentiated the response to DL-AP5 and MK-801. In conclusion, it seems that both NMDA and cholinergic systems not only play a part in the modulation of memory in the dorsal hippocampus of rats but also have demonstrated a complex interaction as well.