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Dinitrobenzene Sulphonic Acid-Induced Colitis Impairs Spatial Recognition Memory in Mice: Roles of N-Methyl D-Aspartate Receptors and Nitric Oxide Publisher Pubmed



Gharedaghi MH1, 2 ; Rahimian R1 ; Dehpour AR1, 3 ; Yousefzadehfard Y1, 4 ; Mohammadifarani A5, 6
Authors

Source: Psychopharmacology Published:2015


Abstract

Rationale: Many peripheral diseases are associated with a decline in cognitive function. In this regard, there have been reports of patients with inflammatory bowel disease and an otherwise unexplained memory impairment. Objectives: We sought to assess the memory performance of mice with colitis. We also investigated the roles of N-methyl d-aspartate (NMDA) receptors and nitric oxide (NO) as possible mediators of colitis-induced amnesia. Methods: To induce colitis, male NMRI mice were intrarectally injected with a solution containing dinitrobenzene sulfonic acid (DNBS; 4 mg in 100 μl) under anesthesia. Three days after intrarectal DNBS instillation, spatial recognition and associative memories were assessed by the Y-maze and passive avoidance tasks, respectively. The NMDA antagonists, MK-801 and memantine, and the inducible NO synthase (iNOS) inhibitor, aminoguanidine, were injected intraperitoneally 45 min before the Y-maze task. Results: Induction of colitis by DNBS impaired spatial recognition memory in the Y-maze task but had no effect on step through latencies in the passive avoidance test. Colitis-induced amnesia was reversed by administering specific doses of MK-801 and memantine (30 μg/kg and 1 mg/kg, respectively) suggesting dysregulated NMDA receptor activation as an underlying mechanism. No effect was seen with lower and higher doses of these drugs, resulting in a bell-shaped dose response curve. Colitis-induced amnesia was also inhibited by aminoguanidine (50 mg/kg), implicating a role for iNOS activation and neuroinflammation in this phenomenon. Conclusion: DNBS-induced colitis impairs memory through NMDA receptor overstimulation and NO overproduction. © 2015 Springer-Verlag Berlin Heidelberg.
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