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Folia Neuropathologica
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vol. 56
Original paper

Interactive involvement of hippocampal cAMP/PKA and cyclooxygenase-2 signaling pathways in spatial learning in the Morris water maze

Kaveh Tabrizian, Mahmoud Hashemzaei, Ali Akbar Nasiri, Sheyda Najafi, Fatemeh Amelinia, Mehdi Sanati, Farzaneh Shamshirgaran, Sahar Fanoudi

Folia Neuropathol 2018; 56 (1): 58-66
Online publish date: 2018/03/28
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Accumulated evidence shows that the cAMP-PKA signaling pathway plays a key role in memory functions. Cyclooxygenase-2, a critical player in neuroinflammation, has been confirmed in the pathogenesis of neurodegenerative diseases. This study is aimed to assess the effect of the interaction of cAMP-PKA and cyclooxygenase pathways on spatial memory acquisition in animal models.

Material 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 spatial memory acquisition in the Morris water maze were investigated. Control animals received bilateral intra-hippocampal 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 on day five.

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.

These results indicate the probable regulatory effects of cAMP/PKA and cyclooxygenase-2 signaling pathways on spatial memory acquisition in the Morris water maze.


COX-2, cAMP/PKA, Morris water maze, spatial memory acquisition, hippocampus

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