Summary
Effects of the 5-HT3 receptor antagonists, ondansetron and tropisetron, on the release of cholecystokipin-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 μg/ml veratrine and was fully Ca2+-dependent and tetrodotoxin-sensitive. Ondansetron and tropisetron, each at 0.1–1 μmol/l, decreased concentration-dependently the veratrine-evoked efflux of CCK-LI. The reduction of CCK-LI output was approximately 30%u when the antagonists were infused at 0.1 μmol/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.
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Correspondence to M. Raiteri at the above address
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Raiteri, M., Paudice, P. & Vallebuona, F. Inhibition by 5-HT3 receptor antagonists of release of cholecystokinin-like immunoreactivity from the frontal cortex of freely moving rats. Naunyn-Schmiedeberg's Arch Pharmacol 347, 111–114 (1993). https://doi.org/10.1007/BF00168781
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DOI: https://doi.org/10.1007/BF00168781