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

Sheri Smith, Hans C. Dringenberg, Brian M. Bennett, Gregory R.J. Thatcher, James N. Reynolds

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

The objective of this study was to test the hypothesis that activation of soluble guanylyl cyclase and increased cGMP formation in the brain would improve task acquisition in cognitively impaired animals. We evaluated the effects of a novel nitrate ester, GT 715 (2,3-dinitrooxy-(2,3-bis-nitrooxy-propyldisulfanyl)-propane), in scopolamine-induced impairment of task acquisition in the Morris water maze. GT 715 improved task acquisition in scopolamine-pretreated animals in a time- and dose-dependent manner, whereas the prototypical nitrate ester, glyceryl trinitrate (GTN), was ineffective. GT 715 also was more effective and more potent than GTN for activation of hippocampal guanylyl cyclase. The results of this study therefore suggest that stimulation of cerebral soluble guanylyl 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. (C) 2000 Lippincott Williams and Wilkins.

Original languageEnglish (US)
Pages (from-to)3883-3886
Number of pages4
JournalNeuroReport
Volume11
Issue number17
DOIs
StatePublished - Nov 27 2000
Externally publishedYes

Keywords

  • Dementia
  • Guanylyl cyclase
  • Hippocampus
  • Morris water maze
  • Nitrate ester
  • Scopolamine

ASJC Scopus subject areas

  • General Neuroscience

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