2-Amino-3-phosphonopropionate blocks the induction and maintenance of long-term potentiation in rat hippocampal slices.

Rat hippocampal slices were used to examine the effects of 2-amino-3-phosphonopropionate (AP3), an inhibitor of phosphatidylinositol (PI) turnover linked to metabotropic quisqualate receptors, on the development and maintenance of long-term potentiation (LTP) in area CA1. When perfused for 5 min prior to tetanization at concentrations of 100-1000 microM, D,L-AP3 had no effect on baseline synaptic transmission but blocked posttetanic potentiation (PTP) and the induction of LTP. Unlike the N-methyl-D-aspartate (NMDA) antagonists, 2-amino-5-phosphonovalerate (AP5) and MK-801, AP3 eliminated the late phase of LTP when applied immediately after tetanization. These data support the hypothesis that PI turnover is a factor in the expression and maintenance of LTP.