Effect of NMDA, a Specific Agonist to NMDA Receptor Complex, on Rat Hippocampus

Removal of Mg2+ ions from perfusion medium provoked epileptiform activity in CA1 field of surviving rat hippocampal slices manifested in generation of extra population spikes. MK-801 (100 mu M), a specific non-competitive antagonist to NMDA-receptor complex, prevented this effect. NMDA (20 mu M), the specific agonist to this complex, produced no significant effect on the orthodromic population spikes, but when applied at concentrations of 30 or 40 mu M, it inhibited them partially (by 21-28%) or almost completely (by 98-99%), correspondingly. Thus, depending on concentration, NMDA can inhibit the synaptic transmission in Schaffer collaterals-hippocampal CA1 pyramidal neurons axis without triggering the epileptiform activity. D-AP5 (50 mu M), a competitive antagonist to NMDA-receptor complex, completely prevented the inhibitory effect of NMDA (40 mu M). While MK-801 (100 mu M) almost completely prevented the inhibitory effect of NMDA, it did not eliminate it when applied after the agonist. Thus, MK-801 can prevent the inhibitory action of NMDA on synaptic transmission in Schaffer collaterals-hippocampal CA1 pyramidal neurons axis via blocking the channel of NMDA-receptor complex, while NMDA exerts its effect only via activation of NMDA receptors.