A novel nitrate ester reverses the cognitive impairment caused by scopolamine in the Morris water maze

The objective of this study was to test the hypothesis that activation of s oluble guanylyl cyclase and increased cGMP formation in the brain would imp rove task acquisition in cognitively impaired animals. We evaluated the eff ects of a novel nitrate ester, GT 715 (2,3-bis-nitrooxy-(2,3-bis-nitrooxy-p ropyldisulfanyl)-propane), in scopolamine-induced impairment of task acquis ition in the Morris water maze. GT 715 improved task acquisition in scopola mine-pretreated animals in a time- and dose-dependent manner, whereas the p rototypical nitrate ester, glyceryl trinitrate (GTN), was ineffective. GT 7 15 also was more effective and more potent than GTN for activation of hippo campal guanylyl cyclase. The results of this study therefore suggest that s timulation of cerebral soluble guanyly cyclase activity may be an effective strategy to improve learning and memory performance in individuals in whom cognitive abilities are impaired by injury, disease, or ageing. NeuroRepor t 11:3883-3886 (C) 2000 Lippincott Williams & Wilkins.