Modulation of the AMPA receptor by phospholipase A2: effect of the antidepressant trimipramine.

Abstract Previous results have shown that chronic administration of the antidepressant trimipramine prevents the formation of long-term potentiation in the rat hippocampus. In the present study, we compared the effects of chronic administration of trimipramine on the binding properties of hippocampal glutamate receptors and on the modulation of the dl -α-amino-3-hydroxy-5- methyl-isoxazolpropionic acid (AMPA) receptors by phospholipase A 2 (PLA 2 ). Whereas the binding characteristics of various agonist and antagonist ligands to the N -methyl- D -aspartate and the AMPA receptors were not modified by trimipramine treatment, there was a significant reduction in the increase in 3 H- AMPA binding elicited by PLA 2 treatment. Since activation of PLA 2 has been reported to play a critical role in the formation of long-term potentiation, possibly mediated through a modification of the AMPA receptors, the results strengthen the hypothesis that PLA 2 -induced modification of 3 H-AMPA binding is an important companent of synaptic plasticity.