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The effects of ondansetron, a 5-HT3 receptor antagonist, on cognition in rodents and primates
J M Barnes1, B Costall, J Coughlan
1Postgraduate Studies in Pharmacology, University of Bradford.
Abstract:
The selective 5-HT3 receptor antagonist, onansetron, has been assessed in three tests of cognition in the mouse, rat and marmoset. In a habituation test in the mouse, ondansetron facilitated performance in young adult and aged animals, and inhibited an impairment in habituation induced by scopolamine, electrolesions or ibotenic acid lesions of the nucleus basalis magnocellularis. Arecoline failed to improve basal performance in young adult mice but inhibited the impairment caused by scopolamine and lesions of the nucleus basalis magnocellularis. In the T-maze reinforced alternation task in rats, ondansetron and arecoline antagonised a scopolamine-induced impairment. In an object discrimination and reversal learning task in the marmoset, assessed using a Wisconsin General Test Apparatus, ondansetron improved performance in a reversal learning task. We conclude that ondansetron potently improves basal performance in rodent and primate tests of cognition and inhibits the impairments in performance caused by cholinergic deficits.
Insights
Ondansetron, a 5-HT3 receptor antagonist, enhances cognitive function in rodents and primates. It improves performance in tasks like habituation and reversal learning, and counteracts cognitive deficits caused by cholinergic system damage.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Cognitive deficits are often linked to cholinergic system dysfunction.
- Selective 5-HT3 receptor antagonists are being investigated for their potential cognitive-enhancing effects.
Purpose of the Study:
- To evaluate the effects of ondansetron on cognitive performance in rodent and primate models.
- To determine if ondansetron can reverse cognitive impairments induced by cholinergic deficits.
Main Methods:
- Ondansetron was tested in habituation, T-maze alternation, and object discrimination/reversal learning tasks.
- Cognitive performance was assessed in mice, rats, and marmosets.
- Cognitive impairments were induced using scopolamine, electrolesions, or ibotenic acid lesions.
Main Results:
- Ondansetron improved basal habituation in young and aged mice.
- Ondansetron and arecoline antagonized scopolamine-induced impairments in rats and mice.
- Ondansetron enhanced reversal learning in marmosets.
Conclusions:
- Ondansetron demonstrates potent cognitive-enhancing effects across species and tasks.
- Ondansetron effectively counteracts cognitive impairments associated with cholinergic deficits.