Verapamil counteracts the masking of long-lasting potentiation of hippocampal population spike produced by 2-amino-5-phosphonovalerate.

In transversely sectioned rat hippocampal slices the effects of 2-amino-5-phosphonovalerate (APV), presumably a selective N-methyl-DL-aspartate antagonist, were examined on the development of long-lasting potentiation (LLP) of the CA1 population spike produced by Schaffer collateral tetanization (100 Hz, 1 s). APF (100 nA, 5 min), when applied 150-200 micron away from the CA1 cell bodies (apical dendritic area), had no significant effect if the population spike was evoked at 0.1 Hz, but produced a depression of the population spike if a 100 Hz tetanus was given during its iontophoresis. This depressant effect of APV was counteracted by verapamil (0.33 microM, 3 min) and LLP induced by the 100 Hz tetanus was unmasked. It is suggested that APV does not antagonize LLP, but only masks it by allowing CA++ influx into CA1 neurones that induces a depression. The results also raise doubts as to the selectivity of APV as an amino acid antagonist.