Different effects of tropisetron and ondansetron in learning and memory paradigms.

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.