THE INFLUENCE OF PERIPHERAL OR CENTRAL ADMINISTRATION OF ONDANSETRON ON STRESS-INDUCED GASTRIC-ULCERATION IN RATS

Ondansetron (0.08, 0.15 or 0.3 mg/kg) injected s.c., every 12 h with t he fourth dose given 0.5 h before experiments, dose-dependently lessen ed gastric glandular mucosal ulceration produced by cold-restraint str ess for 2 h. When given intracerebrally (i.c.) (0.1, 0.5 or I mu g), u sing the same treatment regimen, infusion of ondansetron 1 mu g into t he nucleus amygdaloideus centralis decreased stress-evoked ulcers; in contrast, injection of the same dose into the nucleus accumbens intens ified these lesions. The associated stress-induced stomach wall mast c ell degranulation was unaffected by all s.c. or i.c. doses of ondanset ron. Pretreatment with disodium cromoglycate i.p. alone, or concurrent ly with ondansetron s.c., prevented not only ulceration but also mast cell degranulation. 5-Hydroxytryptamine(3) receptor antagonism appears to inhibit stress-evoked ulcers mainly by blocking the peripheral eff ects of the amine after its release from the gastric mucosal mast cell s.