Dose Dependent Effect Of Memantine On Long-Term Potentiation In The CA1 Area Of The Hippocampus

Document Type : Original Article




Introduction: Generally, NMDA receptor antagonists inhibit learning and long-term potentiation (LTP). However, it has been suggested that direct tonic activation of NMDA receptors, in contrast to learning, may lead to an increase in synaptic “noise”. Uncompetitive NMDA receptor antagonist memantine can paradoxically reverse deficits in learning and synaptic plasticity, and restore LTP impaired by tonic NMDA receptor activation.
Material and Methods: Adult rats weighed 200 to 250g were used in this in vivo study. Stimulating Schaffer collaterals field excitatory postsynaptic potentials (fEPSPs) were evoked in neurons of the CA1 area of the hippocampus. For induction of LTP, high frequency stimulation was applied to the path. Pre- and post-tetanic fEPSPs were recorded extracellularly in the anesthetized rats. Test groups were administered intraperitoneally with memantine (10 mg/kg or20 mg/kg) and the control animals received equal volumes of saline.
Results: Our results express that the drug has no effect on the baseline EPSPs. The tetanic stimulation induced a pronounced LTP in the control group lasting at least 2 hours. The animals treated with 10mg/kg of memantine also displayed a significant LTP; however, the potentiation was lower than the controls. The high frequency stimulation under administration of 20mg/kg of memantine failed to induce LTP in the fEPSPs.
Conclusion: These findings point out a dose dependent attenuation of LTP by memantine. Comparison of the present data and those indicating the ability of memantine to restore LTP led us to conclude that, due to the activation level of the recording path, this moderate affinity NMDA receptor antagonist displays different effects on potentiation of hippocampal recordings.