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Ondansetron and arecoline prevent scopolamine-induced cognitive deficits in the marmoset
G J Carey1, B Costall, A M Domeney
1School of Pharmacy, University of Bradford, UK.
Abstract:
The cognitive-enhancing potential of the 5-hydroxytryptamine (5-HT) selective 5-HT3 receptor antagonist, ondansetron, was investigated in a model of cognitive impairment induced by the muscarinic receptor antagonist, scopolamine. For this purpose, marmosets were trained in an object discrimination task utilizing the Wisconsin General Test Apparatus. Administration of scopolamine (0.01-0.04 mg/kg, SC) caused a dose-dependent impairment in the acquisition of the object discrimination task in that marmosets required more trials to reach criterion, made more errors, and took longer to choose the objects. Administration of arecoline (0.06-0.1 mg/kg, SC) or 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol- 1-yl)methyl]-4H-carbazol-4-one,HCl.2H2O (ondansetron) (0.1-1 micrograms/kg, SC) prevented the scopolamine-induced impairment in task acquisition in that the performance of marmosets was indistinguishable from that of saline-treated animals and was significantly better than that following scopolamine/saline. From these studies, we conclude that ondansetron prevents impairment in the cognitive performance of marmosets induced by administration of scopolamine.
Insights
Ondansetron, a 5-HT3 receptor antagonist, was found to prevent cognitive impairment in marmosets. This drug protected against memory deficits induced by scopolamine, suggesting potential cognitive-enhancing effects.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Cognitive impairment can be induced by muscarinic receptor antagonists like scopolamine.
- The 5-hydroxytryptamine (5-HT) selective 5-HT3 receptor antagonist, ondansetron, has potential cognitive-enhancing properties.
Purpose of the Study:
- To investigate the cognitive-enhancing potential of ondansetron.
- To examine if ondansetron can prevent scopolamine-induced cognitive impairment in marmosets.
Main Methods:
- Marmosets were trained on an object discrimination task using the Wisconsin General Test Apparatus.
- Cognitive impairment was induced using scopolamine (0.01-0.04 mg/kg, SC).
- The effects of ondansetron (0.1-1 micrograms/kg, SC) and arecoline on scopolamine-induced impairment were assessed.
Main Results:
- Scopolamine administration caused a dose-dependent impairment in task acquisition, increasing trials, errors, and choice time.
- Ondansetron and arecoline administration prevented the scopolamine-induced cognitive deficits.
- Performance in the ondansetron and arecoline groups was comparable to saline-treated animals and significantly better than the scopolamine/saline group.
Conclusions:
- Ondansetron effectively prevents cognitive impairment induced by scopolamine in marmosets.
- The 5-HT3 receptor antagonist ondansetron demonstrates potential as a cognitive enhancer.
- These findings highlight the role of 5-HT3 receptors in cognitive processes affected by muscarinic antagonism.