Sex-dependent effect of cyclooxygenase-2 inhibition on mouse spatial memory

Cyclooxygenase (COX)-2 is constitutively expressed in neurons of the hippocampus and neocortex. Therefore, non-steroidal anti-inflammatory drugs (NSAIDs) targeting inflammation-induced COX-2 in the periphery and the central nervous system may also affect cognitive function mediated by basal COX-2 activity. We report that systemic administration of the selective COX-2 inhibitor NS-398 6 h prior to behavioral assessment does not influence spatial acquisition or retention in male C57BL/6J mice. However, we observed impaired spatial retention in female mice treated with NS-398, suggesting a sex-dependent role of COX-2 in spatial memory of mice.