Ascorbic acid attenuates scopolamine-induced spatial learning deficits in the water maze.
Vitamin C (ascorbate) has important antioxidant functions that can help protect against oxidative stress in the brain and damage associated with neurodegenerative disorders such as Alzheimer's disease. When administered parenterally ascorbate can bypass saturable uptake mechanisms in the gut and thus higher tissue concentrations can be achieved than by oral administration. In the present study we show that ascorbate (125 mg/kg) administered intraperitoneally (i.p.) 1-h before testing, partially attenuated scopolamine-induced (1 mg/kg i.p.) cognitive deficits in Morris water maze performance in young mice. Cumulative search error, but not escape latency nor path length, was significantly improved during acquisition in ascorbate plus scopolamine-treated mice although performance did not equal that of control mice. During the probe trial, scopolamine led to increased search error and chance level of time spent in the platform quadrant, whereas mice pre-treated with ascorbate prior to scopolamine did not differ from control mice on these measures. Ascorbate had no effect on unimpaired, control mice and neither did it reduce the peripheral, activity-increasing effects of scopolamine. Ascorbate alone increased acetylcholinesterase activity in the medial forebrain area but had no effect in cortex or striatum. This change, and its action against the amnestic effects of the muscarinic antagonist scopolamine, suggest that ascorbate may be acting in part via altered cholinergic signaling. However, further investigation is necessary to isolate the cognition-enhancing effects of ascorbate.
Harrison
F E
FE
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Fiona.Harrison@Vanderbilt.edu
Hosseini
A H
AH
Dawes
S M
SM
Weaver
S
S
May
J M
JM
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004924:Escape Reaction / Q000187:drug effects; D005260:Female; D007859:Learning Disabilities / Q000139:chemically induced / Q000188:drug therapy*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D018697:Nootropic Agents / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D012601:Scopolamine; D013028:Space Perception / Q000187:drug effects*; D013997:Time Factors
D018697:Nootropic Agents; D012601:Scopolamine; D000110:Acetylcholinesterase; D001205:Ascorbic Acid
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