Combined administration of subthreshold doses of the nitric oxide inhibitor, nitro-L-arginine, and muscarinic receptor antagonist, scopolamine, impairs complex maze learning in rats.
Traditionally, research into the neurobiological mechanisms of age-related memory impairments has focused on single neurotransmitter systems. As normal and abnormal age-related declines in memory function probably involve alterations in more than one system, a more effective approach for elucidating underlying neurobiological changes and resulting impairments may be to evaluate the roles of multiple systems simultaneously. This study evaluated the interaction of the cholinergic and nitric oxide systems in rats on acquisition in the 14-unit T-maze. This task requires learning a series of turns to avoid foot shock, and most likely reflects procedural learning. Administration of scopolamine (0.1 mg/kg) or N-nitro-L-arginine methyl ester (30 mg/kg) alone did not impair acquisition, whereas administration of the same doses in combination increased both the latency to complete the maze and number of errors committed. These data suggest that manipulation of learning and memory processes with multiple compounds potentially offers a clinically relevant paradigm for investigating cognitive function in normal and abnormal aging.
Pistell
Paul J
PJ
Behavioral Neuroscience Section, Laboratory of Experimental Gerontology, National Institute on Aging, National Institutes of Health, Gerontology Research Center, Baltimore, Maryland, USA. Paul.Pistell@pbrc.edu
Daffin
Lee W
LW
Nelson
Christopher M
CM
Duffy
Kara B
KB
Bowker
Jonna L
JL
Spangler
Edward L
EL
Ingram
Donald K
DK
Devan
Bryan D
BD
D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D003071:Cognition; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D011916:Rats, Inbred F344; D012601:Scopolamine / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D009569:Nitric Oxide; D012601:Scopolamine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester