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Different effects of tropisetron and ondansetron in learning and memory paradigms
1Department of Biology, Boehringer Ingelheim Italia, Milano, Italy.
Abstract:
The effects of the 5-HT3 receptor antagonists tropisetron (ICS 205-930) and ondansetron on memory and performance impairments induced by scopolamine were tested in a passive avoidance procedure and in the Morris water maze task. Pretreatment with ondansetron (0.01 and 1 microgram/kg i.p.) but not with tropisetron (1, 10, and 30 micrograms/kg i.p.) reversed scopolamine-induced memory deficits in the step-through passive avoidance task. When the effects of these 5-HT3 receptor antagonists on cognition were assessed in the Morris water maze, ondansetron (0.01, 1, and 10 micrograms/kg i.p.) did not antagonize scopolamine-induced spatial navigation deficits. On the contrary, pretreatment with tropisetron (10 and 30 micrograms/kg, and to some extent also with 1 microgram/kg i.p.) counteracted the learning and memory impairment due to scopolamine treatment. The findings suggest that it could be worthwhile to investigate whether or not different subtypes of the 5-HT3 receptor may underlie the different effects on cognition displayed by compounds that belong to the same pharmacological class.
Insights
Ondansetron and tropisetron, 5-HT3 receptor antagonists, showed differing effects on scopolamine-induced memory impairments. Tropisetron improved cognitive deficits in the Morris water maze, while ondansetron aided in passive avoidance tasks.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Scopolamine is known to induce memory and performance impairments.
- 5-HT3 receptor antagonists are investigated for their potential cognitive-enhancing effects.
Purpose of the Study:
- To evaluate the effects of tropisetron and ondansetron on scopolamine-induced cognitive deficits.
- To determine if these 5-HT3 receptor antagonists can reverse memory and performance impairments.
Main Methods:
- Utilized a step-through passive avoidance task and the Morris water maze task.
- Administered scopolamine to induce cognitive deficits, followed by pretreatment with tropisetron or ondansetron.
- Assessed memory and spatial navigation performance in rodents.
Main Results:
- Ondansetron reversed scopolamine-induced memory deficits in the passive avoidance task.
- Tropisetron counteracted learning and memory impairment in the Morris water maze task.
- Ondansetron did not antagonize scopolamine-induced spatial navigation deficits.
Conclusions:
- Different 5-HT3 receptor antagonists exhibit distinct effects on cognition.
- Subtypes of the 5-HT3 receptor may be responsible for these varied cognitive effects.
- Further research into 5-HT3 receptor subtypes is warranted to understand their role in cognition.