Arachidonic acid rescues hippocampal long-term potentiation blocked by group I metabotropic glutamate receptor antagonists

Although there is evidence that group T metabotropic glutamate receptors participate in long-term potentiation, the role of these receptors remains unclear. Among antagonists of group I metabotropic glutamate receptors, the mGluR5-selective 6-methyl-2-(phenplethynyl)-pyridine inhibited long-term potentiation in the CA1 region of hippocampal slices from 30-day-old rats, whereas (RS)-1-aminoindan-1,5-dicarboxylic acid and cyclopropan[b]chromen-1a-carboxylic acid ethylester, which are more selective for mGluR1, failed to inhibit long-term potentiation. Evidence also indicates that arachidonic acid is required for long-term potentiation, as inhibition of phospholipase A(2) blocks long-term potentiation. Administration of arachidonic acid immediately after tetanic stimulation restored long-term potentiation that had been inhibited by group I antagonist. Furthermore, arachidonic acid overcame inhibition of long-term potentiation by xestospongin C, an inositol triphosphate receptor channel blocker, or by thapsigargin, an agent that depletes intracellular calcium stores. However, arachidonic acid did not restore longterm potentiation blocked by N-methyl-D-aspartate receptor antagonists. Although it has been assumed that the source of the arachidonic acid necessary for long-term potentiation is N-methyl-D-aspartate receptor activation, our results suggest that during long-term potentiation group I metabotropic glutamate receptors cause arachidonic acid release by mobilization of intracellular calcium. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.