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

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.