Interactive Involvement of Hippocampal cAMP/ PKA and Cyclooxygenase-2 Signaling Pathways in Spatial Learning in the Morris Water Maze

Accumulated evidence shows that the cAMP-PKA signaling pathway plays a key role in memory functions. Cyclooxygenase-2, a criticalplayer in neuroinflammation, has been confirmed in the pathogenesis of neurodegenerative diseases. This study is aimed to assess the effect of the interaction of cAMPPKA and cyclooxygenase pathways on spatial memory acquisition in animal models. Materials and Methods:In the present study, the effects of the four-day bilateral intra-hippocampal infusions of H-89 as a protein kinase AII inhibitor (10 μM/side), celecoxib (0.1 M/side) as a selective cyclooxygenase-2 inhibitor, celecoxib/H-89 and bucladesine (10 μM/side)/celecoxib/H-89 on spatialmemory acquisition in the Morris water maze were investigated. Control animals received bilateral intrahippocampal infusions of dimethyl sulfoxide. Rats were trained for 4 days; each day included one block of four trials. Post-training probe trial tests were performed onday five. Results: A bilateral intra-hippocampal infusion of H-89 and celecoxib led to a significant impairment in spatial learning compared to the controls through a notable decrease in escape latency and traveled distance. But, combination treatment of animals with celecoxib/H-89 and bucladesine/celecoxib/H-89 could considerably reverse celecoxib and H-89-induced spatial memory acquisition impairments in the Morris water maze. Conclusion: These results indicate the probable regulatory effects of cAMP/PKA and cyclooxygenase-2 signaling pathways on spatial memory acquisition in the Morris water maze.