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 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 (delta 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, delta 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.
Dépôt
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Department of Pharmacology, Faculty of Medicine, Université de Montréal, Quebec, Canada.
Caillé
G
G
Mukherjee
J
J
Katzman
M A
MA
Cadieux
A
A
Bradwejn
J
J
D000293:Adolescent; D000328:Adult; D001519:Behavior / Q000187:drug effects*; D004311:Double-Blind Method; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009490:Neurosecretory Systems / Q000187:drug effects*; D017294:Ondansetron / Q000008:administration & dosage / Q000494:pharmacology; D011388:Prolactin / Q000097:blood; D011985:Receptors, Serotonin / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D013758:Tetragastrin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D013758:Tetragastrin; D019382:Human Growth Hormone; D017294:Ondansetron; D011388:Prolactin; D006854:Hydrocortisone