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 sys tem using 9-anthryldiazomethane (ADAM) as a fluorescent probe. High frequen cy stimulation (tetanic stimulation) to a hippocampal slice from the guinea pig brain caused a huge increase in the release of glutamate from presynap tic 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 sele ctive AMPA/kainate receptor antagonist, DNQX, or to a lesser extent by the selective NMDA receptor antagonist, APV, These findings suggest that arachi donic acid is produced by activation of ionotropic glutamate receptors invo lving expression of LTP, Arachidonic acid exerted a longlasting facilitator y action on synaptic transmission in the CA1 region of rat hippocampal slic es and the facilitation occluded the tetanic LTP. Arachidonic acid, thus, a ppears to be a significant factor for the expression of LTP. (C) 1999 Acade mic Press.