WE compared the interaction between the metabotropic glutamate receptor agonist ACPD and arachidonic acid with the interaction between ACPD and nerve growth factor (NGF) on presynaptic function in hippocampus. ACPD interacted with both NGF and arachidonic acid to increase KCl-stimulated endogenous glutamate release and calcium concentration in synaptosomes prepared from whole hippocampus and synaptosomes prepared from untetanized dentate gyrus. The data indicate that prior induction of long-term potentiation (LTP) in perforant path granule cells synapses occluded the interaction between ACPD and both NGF and arachidonic acid, suggesting that these agents may play a role in the generation of LTP in dentate gyrus.