Cyclooxygenase i and II inhibitors distinctly enhance hippocampal- and cortex-dependent cognitive functions in mice

Abstract

Cyclooxygenase (COX) enzymes are expressed in the brain; however, their role in hippocampus-dependent and cortex-dependent cognitive functions remains to be fully elucidated. The aim of the present study was to comparatively investigate the effects of piroxicam, a selective COX-I inhibitor, and celecoxib, a selective COX-II inhibitor, on cognitive functions in an AlCl3-induced neurotoxicity mouse model to understand the specific role of each COX enzyme in the hippocampus and cortex. The AlCl3 (250 mg/kg) was administered to the mice in drinking water and the drugs were administered in feed for 30 days. Assessments of memory, including a Morris water maze, social behavior and nesting behavior were performed in control and treated mice. The RNA expression of the COX enzymes were analyzed using reverse transcription-quantitative polymerase chain reaction analysis. An ex-vivo 2,2-Diphenyl-1-picrylhydrazyl assay was performed in the hippocampus and cortex. Following 30 days of treatment with thedrugs, the mice in the celecoxib- and piroxicam-treated groups exhibited enhanced learning (6.84±0.76 and 9.20±1.08, respectively), compared with the AlCl3-induced neurotoxicity group (21.14±0.76) on the fifth day of the Morris water maze test. Celecoxib treatment improved social affiliation in the AlCl3-induced neurotoxicity group, the results of which were superior to piroxicam. Piroxicam led to better improvement in nesting score in the AlCl3-induced neurotoxicity group. Both drugs decreased the expression levels of COX-I and COX-II in the hippocampus and cortex, and rescued oxidative stress levels. These findings suggested that each drug distinctly affected cognitive functions, highlighting the distinctive roles of COX-I and COX-II in learning and memory.