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Original Article |
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Neuropsychopharmacology (1999) 20 177-187.10.1038/sj.npp.1395257
Acute and Chronic Role of 5-HT3 Neuronal System on Behavioral and Neuroendocrine Changes Induced by Intravenous Cholecystokinin Tetrapeptide Administration in Humans
Michelle Dépôt1 Ph.D, Gilles Caillé1 Ph.D, Jayanti Mukherjee2 Ph.D, Martin A Katzman3 MD, Alain Cadieux4 Ph.D and Jacques Bradwejn3 MD |
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1Department of Pharmacology, Faculty of Medicine, Université de Montreéal, Montreal, Quebec, Canada
2Bristol-Myers Squibb, Ville St-Laurent, Quebec, Canada
3The Clarke Institute of Psychiatry, University of Toronto, Toronto, Ontario, Canada
4Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada
Correspondence: Dr Michelle Dépôt, Université de Montréal, Faculty of Medicine, Department of Pharmacology, C.P. 6128, Succ. Centre-ville, Main Building, R-401, Montreal, Quebec, Canada, H3C 3J7
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ABSTRACT
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The influence of single and multiple oral doses of ondansetron, a selective 5-HT3 receptor antagonist, was evaluated against placebo on cholecystokinin tetrapeptide (CCK-4)-induced behavioral and neuroendocrine changes in humans. 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 significantly higher and maximal changes in cortisol, growth hormone, and prolactin secretion from baseline ( max) were significantly lower in the ondansetron group. After ondansetron and placebo chronic administration, there were no statistical differences in the iPSS between groups. Pre-CCK-4 NPY plasma levels were significantly higher; whereas, max for NPY significantly lower in the ondansetron group as compared to placebo. These results suggest a role for the 5-HT3 receptor in the neurobiology of panic disorder through a possible interaction with CCK and NPY systems. Ondansetron chronic effect on CCK-4-induced behavioral changes needs further exploration.
Keywords: Ondansetron; Cholecystokinin tetrapeptide (CCK-4); Panic disorder; ACTH; Cortisol; Growth hormone; Neuropeptide Y; Prolactin |
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