MODULATION OF THE AMPA RECEPTOR BY PHOSPHOLIPASE A(2) - EFFECT OF THEANTIDEPRESSANT TRIMIPRAMINE

Previous results have shown that chronic administration of the antidep ressant 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 L-alpha- amino-3-hydroxy-5-methyl-isoxazolpropionic acid (AMPA) receptors by ph ospholipase A(2) (PLA(2)). Whereas the binding characteristics of vari ous 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 H-3-AMPA binding elicited by PLA(2) treatment. Since activation of PLA(2) has been reported to p lay a critical role in the formation of long-term potentiation, possib ly mediated through a modification of the AMPA receptors, the results strengthen the hypothesis that PLA(2)-induced modification of H-3-AMPA binding is an important component of synaptic plasticity.