dizocilpine-maleate and Colitis

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.

Topics: Animals; Avoidance Learning; Benzenesulfonates; Cognition; Colitis; Dizocilpine Maleate; Guanidines; Male; Memantine; Memory Disorders; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Receptors, N-Methyl-D-Aspartate; Spatial Memory

Inhibition of somatic nociception by conditioning noxious visceral stimulation was studied under pathophysiological conditions in rats. Viscero-somatic inhibition was enhanced following visceral inflammation and reduced by a somatic heat injury. The enhancement was reversed by an N-methyl-D-aspartate (NMDA) receptor antagonist. These changes in viscero-somatic inhibition may be explained by corresponding changes in excitatory drives evoked by conditioning and test stimulation, although disinhibition may contribute to reduction of inhibition following somatic injury.

Topics: Animals; Burns; Colitis; Colon; Conditioning, Psychological; Dizocilpine Maleate; Down-Regulation; Excitatory Amino Acid Antagonists; Hyperalgesia; Inflammation; Male; Neural Inhibition; Nociceptors; Pain; Physical Stimulation; Rats; Rats, Wistar; Reaction Time; Receptors, N-Methyl-D-Aspartate; Rectum; Reflex; Skin; Synaptic Transmission; Visceral Afferents