Ondansetron improves cognitive performance in the Morris water maze spatial navigation task

In the present studies we investigated the actions of ondansetron, a prototypic 5-hydroxytryptamine3 (5-HT3) receptor antagonist, on performance in a complex spatial navigation/memory task in rats. Specifically, we compared the activity of ondansetron to that of the cholinesterase inhibitor physosti...

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Published in:Psychopharmacologia 1995-08, Vol.120 (4), p.409-417
Main Authors: FONTANA, D. J, DANIELS, S. E, HENDERSON, C, EGLEN, R. M, WONG, E. H. F
Format: Article
Language:English
Subjects:
Animals
Atropine - pharmacology
Biological and medical sciences
Cognition - drug effects
Dose-Response Relationship, Drug
Female
Male
Maze Learning
Medical sciences
Memory - drug effects
Neuropharmacology
Ondansetron - pharmacology
Pharmacology. Drug treatments
Physostigmine - pharmacology
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Rats
Rats, Sprague-Dawley
Rats, Wistar
Spatial Behavior - drug effects
Time Factors
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Summary:In the present studies we investigated the actions of ondansetron, a prototypic 5-hydroxytryptamine3 (5-HT3) receptor antagonist, on performance in a complex spatial navigation/memory task in rats. Specifically, we compared the activity of ondansetron to that of the cholinesterase inhibitor physostigmine in attenuating two distinct cognitive deficits in the Morris water maze. In the first model, rats treated with the muscarinic receptor antagonist atropine (30 mg/kg) had significantly longer latencies to find the submerged platform across two days of testing. Physostigmine (0.03, 0.1 and 0.3 mg/kg) and ondansetron (0.03-1 mg/kg) significantly reduced the latencies to find the submerged platform in atropine-treated animals, suggesting an increase in cognitive performance. There was little evidence of a dose-response relationship for either compound, and a loss of efficacy for ondansetron was seen at 3 mg/kg. In the second model, pre-screened, aged (23 months), cognition-impaired and nonimpaired rats were tested. Ondansetron (0.1 mg/kg), but not physostigmine (0.1 mg/kg), decreased the latencies to find the submerged platform in the aged-impaired rats, while neither compound improved performance of aged-nonimpaired rats. These data suggest that ondansetron may have cognition enhancing properties in animal models of aging and cholinergic hypofunction.
ISSN:0033-3158
1432-2072
DOI:10.1007/BF02245812