Abstract
The serotonin 5-HT 3 receptor antagonists ondansetron and SEC-579 were tested over a wide dose range (0.000001–0.5 mg/kg, PO) for cognitive-enhancing effects in aged rhesus monkeys. Animals were tested on the following cognitive and motor tasks: 1) acquisition of a visual object discrimination; 2) reversal of a visual object discrimination; 3) the delayed response task, a spatial working memory task; and 4) a fine motor task. This study found enhanced acquisition of a visual object discrimination following very low doses (0.000001–0.00001 mg/kg, PO) of either 5-HT 3 receptor antagonist. This finding replicates a previous study in marmosets (14). However, unlike the marmoset research, no reliable improvement was found on the reversal condition. Similarly, no improvement was observed on the delayed response or fine motor tasks. No side effects were observed at any dose, consistent with reports in both animals and humans. These results suggest that 5-HT 3 receptor antagonists may be helpful treating a subset of cognitive functions.
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