Arachidonic acid as a messenger for the expression of long-term potentiation.

Arachidonic acid is suggested to play a role in the expression of long-term potentiation (LTP), a synaptic analog of memory and learning. However, it is unknown whether this free fatty acid is actually released during LTP or not. To address this question, we assayed arachidonic acid with an HPLC system using 9-anthryldiazomethane (ADAM) as a fluorescent probe. High frequency stimulation (tetanic stimulation) to a hippocampal slice from the guinea pig brain caused a huge increase in the release of glutamate from presynaptic terminals and in turn, a gradual increase in the release of arachidonic acid. A similar increase in the release of arachidonic acid was induced by application of glutamate and the increase was inhibited by either the selective AMPA/kainate receptor antagonist, DNQX, or to a lesser extent by the selective NMDA receptor antagonist, APV. These findings suggest that arachidonic acid is produced by activation of ionotropic glutamate receptors involving expression of LTP. Arachidonic acid exerted a long-lasting facilitatory action on synaptic transmission in the CA1 region of rat hippocampal slices and the facilitation occluded the tetanic LTP. Arachidonic acid, thus, appears to be a significant factor for the expression of LTP. Copyright 1999 Academic Press.