The effects of 5-HT3 receptor antagonists on cognitive performance in aged monkeys.
The serotonin 5-HT3 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-HT3 receptor antagonist. This finding replicates a previous study in marmosets. 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-HT3 receptor antagonists may be helpful in treating a subset of cognitive functions.
Arnsten
A F
AF
Section of Neurobiology, Yale Medical School, New Haven 06510-8001, USA.
Lin
C H
CH
Van Dyck
C H
CH
Stanhope
K J
KJ
D000375:Aging / Q000523:psychology*; D000818:Animals; D003071:Cognition / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology; D004192:Discrimination, Psychological / Q000187:drug effects / Q000502:physiology; D005260:Female; D008253:Macaca mulatta; D009042:Motivation; D009044:Motor Cortex / Q000187:drug effects / Q000254:growth & development; D017294:Ondansetron / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects*; D015363:Quinolones / Q000494:pharmacology*; D012193:Reversal Learning / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014796:Visual Perception / Q000187:drug effects / Q000502:physiology
D015363:Quinolones; D012702:Serotonin Antagonists; D017294:Ondansetron; C104926:mirisetron