COX-2, but not COX-1, activity is necessary for the induction of perforant path long-term potentiation and spatial learning in vivo.
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 brain in 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, PGE(2), 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 PGE(2) resulting from COX-2 but not COX-1 activity are necessary for synaptic plasticity and memory acquisition.
Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland.
T R
TR
Cowley
B
B
Fahey
S M
SM
O'Mara
D000818:Animals; D051545:Cyclooxygenase 1 / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology*; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D008569:Memory Disorders / Q000201:enzymology / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology; D019580:Perforant Pathway / Q000201:enzymology*; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013028:Space Perception / Q000502:physiology*; D013569:Synapses / Q000201:enzymology; D009435:Synaptic Transmission / Q000502:physiology
D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D016760:Proto-Oncogene Proteins c-fos; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D048049:Extracellular Signal-Regulated MAP Kinases; D015232:Dinoprostone