Arachidonic acid rescues hippocampal long-term potentiation blocked by group I metabotropic glutamate receptor antagonists.
Although there is evidence that group I 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-(phenylethynyl)-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 antagonists. 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 long-term 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.
Izumi
Y
Y
Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA. izumiy@psychiatry.wustl.edu
Zarrin
A R
AR
Zorumski
C F
CF
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000502:physiology
D018094:Receptors, Metabotropic Glutamate; D016718:Arachidonic Acid; D002118:Calcium