A time course analysis of cyclooxygenase-2 suggests a role in spatial memory retrieval in rats.

We previously showed a role for COX-2 in spatial memory retention. In that study we investigated the effects of post-training intrahippocampal infusion of celecoxib as a COX-2-specific inhibitor on spatial memory retention. Those infusions impaired spatial memory retention in the Morris water maze. In the present study a time course analysis of role of COX-2 in spatial memory was conducted. Here stereotaxic surgery was employed for the bilateral implantation of guide cannulas into the CA1 region of the hippocampus. Training trials were started after recovery of the animals. Immediately after last trial of training on third day, the celecoxib (0.1M) was infused bilaterally and testing trials, were performed 1, 2, 3, and 7 days after celecoxib infusions. Significant alterations were observed in escape latency and traveled distance 2 and 3 days after celecoxib infusions. The maximum impairment was obtained 72 h after the infusions. The data suggests that the effect of celecoxib is transient and that its effect on performance is likely caused by a problem in memory retrieval. Quantification analyses of the immunostaining of COX-2-containing neurons in the dorsal hippocampus show that celecoxib infusions significantly reduced (P<0.05) COX-2 immunoreactivity for the animals that were tested 3 days after the drug infusion. Results from the behavioral study along with the findings from immunohistochemical analyses suggest that COX-2 has significant role in spatial memory retrieval. Moreover, the memory deficits induced by the infusions continuously persists for 3 days.