Evidence for the involvement of neuronal nitric oxide synthase and soluble guanylate cyclase on cognitive functions in rats

Aims: The influence of 3-bromo-7-nitroindazole (3-Br 7-NI), a potent and selective neuronal nitric oxide synthase (nNOS) inhibitor, and [1H-[1,2,4]-oxadiazole[4,3a]-quinoxaline-1-one] (ODQ), a highly selective, irreversible inhibitor of soluble guanylate cyclase (sGC), on working and reference memory and emotional learning was investigated in rats. Main methods: The effects were assessed in the three-panel runway and step-down passive avoidance task. respectively. Key findings: 3-Br 7-NI (5, 10, and 20 mg/kg) and ODQ (5, 10, and 20 mg/kg) significantly increased the number of errors and latency of both working and reference memory performance of rats and impaired retention for the passive avoidance task. The effect of 3-Br 7-NI was reversed by L-arginine (250 mg/kg). Significance: Findings of the study supported the hypothesis that nNOS inhibition disrupts reference and working memory processes in terms of an impairment in the strategies used for solving learning tasks, and, according to these results, nNOS-sGC may be required for emotional learning and both reference and working memory. (C) 2011 Elsevier Inc. All rights reserved.