title: Post-training cyclooxygenase-2 (COX-2) inhibition impairs memory consolidation.
abstract: Evidence indicates that prostanoids, such as prostaglandins, play a regulatory role in several forms of neural plasticity, including long-term potentiation, a cellular model for certain forms of learning and memory. In these experiments, the significance of the COX isoforms cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in post-training memory processes was assessed. Adult male Long-Evans rats underwent an eight-trial (30-sec intertrial interval) training session on a hippocampus-dependent (hidden platform) or dorsal striatal-dependent (visible platform) tasks in a water maze. After the completion of training, rats received an intraperitoneal injection of the nonselective COX inhibitor indomethacin, the COX-1-specific inhibitor piroxicam, the COX-2-specific inhibitor N-[2-cyclohexyloxy-4-nitrophenyl]-methanesulfonamide (NS-398), vehicle (45% 2-hydroxypropyl-beta-cyclodextrin in distilled water), or saline. On a two-trial retention test session 24 h later, latency to mount the escape platform was used as a measure of memory. In the hidden platform task, the retention test escape latencies of rats administered indomethacin (5 and 10 mg/kg) or NS-398 (2 and 5 mg/kg) were significantly higher than those of vehicle-treated rats, indicating an impairment in retention. Injections of indomethacin or NS-398 that were delayed 2 h post-training had no effect on retention. Post-training indomethacin or NS-398 had no influence on retention of the visible platform version of the water maze at any of the doses administered. Furthermore, selective inhibition of COX-1 via post-training piroxicam administration had no effect on retention of either task. These findings indicate that COX-2 is a required biochemical component mediating the consolidation of hippocampal-dependent memory.
authors.affiliation: Neuroscience Center of Excellence, Louisiana State University Health Center, New Orleans, LA 70112, USA. lteather@mit.edu
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Teather
authors.forename: Mark G
authors.initials: MG
authors.lastname: Packard
authors.forename: Nicolas G
authors.initials: NG
authors.lastname: Bazan
mesh_terms: D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D007858:Learning / Q000187:drug effects / Q000502:physiology; D008297:Male; D008565:Membrane Proteins; D008568:Memory / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D009578:Nitrobenzenes / Q000494:pharmacology; D010894:Piroxicam / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D010894:Piroxicam; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D007213:Indomethacin