Acute and chronic role of 5-HT3 neuronal system on behavioral and neuroendocrine changes induced by intravenous cholecystokinin tetrapeptide administration in humans

The influence of single and multiple oval doses of ondansetron, a selective 5-HT3 receptor antagonist, was evaluated against placebo on cholecystokini n tetrapeptide (CCK-4)-induced behavioral and neuroendocrine changes in hum ans. As compared to placebo, subjects receiving acute ondansetron treatment showed a significant decrease in the sum intensity of CCK-4-induced-panic symptoms (iPSS). Pre-CCK-4 neuropeptide Y (NPY) plasma levels were signific antly higher and maximal changes in cortisol, growth hormone, and prolactin secretion from baseline (Delta(max)) were significantly lower in the ondan setron group. After ondansetron and placebo chronic administration, there w ere ilo statistical differences in the iPSS between groups. Pre-CCK-4 NPY p lasma levels were significantly higher; whereas, Delta(max) for NPY signifi cantly lower in the ondansetron group as compared to placebo. These results suggest a role for the 5-HT3 receptor in the neurobiology of panic disorde r through a possible interaction with CCK and NPY systems. Ondansetron chro nic effect on CCK-4-induced behavioral changes needs further exploration. [ Neuropsychopharmacology 20:177-187, 1999] (C) 1998 American College of Neur opsychopharmacology. Published by Elsevier Science Inc.