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

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-alpha-amino-3-hydroxy-5- methyl-isoxazolpropionic acid (AMPA) receptors by phospholipase A2 (PLA2). 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 3H-AMPA binding elicited by PLA2 treatment. Since activation of PLA2 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 PLA2-induced modification of 3H-AMPA binding is an important component of synaptic plasticity.