Inhibition by 5-HT3 receptor antagonists of release of cholecystokinin-like immunoreactivity from the frontal cortex of freely moving rats.
Effects of the 5-HT3 receptor antagonists, ondansetron and tropisetron, on the release of cholecystokinin-like immunoreactivity (CCK-LI) in rat frontal cortex were investigated in conscious, unrestrained rats using intracerebral microdialysis. The release of CCK-LI was augmented by perfusion with 100 micrograms/ml veratrine and was fully Ca(2+)-dependent and tetrodotoxin-sensitive. Ondansetron and tropisetron, each at 0.1-1 mumol/l, decreased concentration-dependently the veratrine-evoked efflux of CCK-LI. The reduction of CCK-LI output was approximately 30% when the antagonists were infused at 0.1 mumol/l. The data suggest that 5-HT3 receptor antagonists prevent the release of CCK evoked by endogenous 5-hydroxytryptamine. These drugs may thus represent a novel therapeutic approach in disease states, like anxiety, in which an inappropriately high release of brain CCK or 5-hydroxytryptamine seems to be involved.
Raiteri
M
M
Istituto di Farmacologia e Farmacognosia, Università degli Studi di Genova, Italia.
Paudice
P
P
Vallebuona
F
F
D000818:Animals; D002766:Cholecystokinin / Q000378:metabolism*; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists; D000077526:Tropisetron; D014702:Veratrine / Q000494:pharmacology
D007211:Indoles; D012702:Serotonin Antagonists; D017294:Ondansetron; D000077526:Tropisetron; D002766:Cholecystokinin; D014702:Veratrine