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.