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 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-nitrooxypropyldisulfanyl)-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.
Smith
S
S
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
Dringenberg
H C
HC
Bennett
B M
BM
Thatcher
G R
GR
Reynolds
J N
JN
D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D006162:Guanylate Cyclase / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D018727:Muscarinic Antagonists / Q000633:toxicity*; D009566:Nitrates / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D011407:Propane / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012601:Scopolamine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D014665:Vasodilator Agents / Q000494:pharmacology
C420322:GT 715; D018727:Muscarinic Antagonists; D009566:Nitrates; D014665:Vasodilator Agents; D012601:Scopolamine; D006162:Guanylate Cyclase; D005996:Nitroglycerin; D011407:Propane