COX‐2, but not COX‐1, activity is necessary for the induction of perforant path long‐term potentiation and spatial learningin vivo

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Abstract
The objectives of this research were to investigate the role played by the enzyme cyclooxygenase (COX) in learning and memory, synaptic plasticity and synaptic transmission in the rat brainin vivo. Male Wistar rats were treated with isoform‐selective inhibitors for COX‐1 and COX‐2, either chronically and tested in the watermaze or acutely before electrophysiological recordings were made. We found a significant impairment in acquisition of the watermaze with inhibition of COX‐2. Furthermore, we found COX‐2 but not COX‐1 inhibition significantly blocked long‐term potentiation (LTP) induction but had no effect on already established LTP. Moreover, exogenous replacement of the main metabolite of COX‐2 activity, PGE2, was sufficient to restore LTP induction and for normal downstream signalling to ensue, namely extracellular signalling‐regulated kinase (ERK)‐phosphorylation and c‐FOS expression. We conclude that endogenous basal levels of PGE2resulting from COX‐2 but not COX‐1 activity are necessary for synaptic plasticity and memory acquisition.