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.
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Acknowledgments
This study was supported by a grant from the Vice Chancellor of Research of Kermanshah University of Medical Sciences. The protocol for this study was approved by our institution’s animal use and care committee (Department of Pharmacology, Kermanshah University of Medical Sciences, Kermanshah, Iran), and the experiments were performed in accordance with Iranian laws.
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The authors declare no conflict of interests.
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Mohammad Hadi Gharedaghi and Reza Rahimian contributed equally to this work.
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Gharedaghi, M.H., Rahimian, R., Dehpour, A.R. et al. Dinitrobenzene sulphonic acid-induced colitis impairs spatial recognition memory in mice: roles of N-methyl D-aspartate receptors and nitric oxide. Psychopharmacology 232, 3081–3090 (2015). https://doi.org/10.1007/s00213-015-3950-x
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DOI: https://doi.org/10.1007/s00213-015-3950-x