, Volume 232, Issue 16, pp 3081–3090 | Cite as

Dinitrobenzene sulphonic acid-induced colitis impairs spatial recognition memory in mice: roles of N-methyl D-aspartate receptors and nitric oxide

  • Mohammad Hadi Gharedaghi
  • Reza Rahimian
  • Ahmad Reza DehpourEmail author
  • Yashar Yousefzadeh-Fard
  • Ahmad Mohammadi-FaraniEmail author
Original Investigation



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.


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.


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.


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.


DNBS-induced colitis impairs memory through NMDA receptor overstimulation and NO overproduction.


Dinitrobenzene sulfonic acid-induced colitis Y-maze paradigm Memory N-methyl d-aspartate MK-801 Memantine Nitric oxide Aminoguanidine Passive avoidance test Mice 



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.

Conflict of interest

The authors declare no conflict of interests.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Mohammad Hadi Gharedaghi
    • 1
    • 2
  • Reza Rahimian
    • 1
  • Ahmad Reza Dehpour
    • 1
    • 3
    Email author
  • Yashar Yousefzadeh-Fard
    • 1
    • 4
  • Ahmad Mohammadi-Farani
    • 5
    • 6
    Email author
  1. 1.Department of Pharmacology, School of MedicineTehran University of Medical SciencesTehranIran
  2. 2.Department of SurgeryMassachusetts General Hospital, Harvard Medical SchoolBostonUSA
  3. 3.Experimental Medicine Research CenterTehran University of Medical SciencesTehranIran
  4. 4.Division of Molecular Imaging and Neuropathology, Department of PsychiatryNew York State Psychiatry Institute, Columbia University Medical CenterNew YorkUSA
  5. 5.Novel Drug Delivery Research CenterKermanshah University of Medical SciencesKermanshahIran
  6. 6.Department of Pharmacology, Toxicology and Medical Services, Faculty of PharmacyKermanshah University of Medical SciencesKermanshahIran

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