A benzodiazepine receptor inverse agonist inhibits stress-induced ulcer formation

The effects of a benzodiazepine receptor inverse agonist (FG 7142) on gastric ulcer formation were studied in restrained rats. FG 7142 (10-50 mg/kg) reduced in a dose-dependent fashion both the number and cumulative length of gastric ulcers elicited by restraint for 2 hr at 4 degrees C, but did not affect ulcer formation in unrestrained animals maintained in this environment. FG 7142 also reduced gastric ulcer formation in restrained rats maintained at 22 degrees C for 5 hr. The ability of FG 7142 to reduce restraint-stress induced gastric ulcer formation was blocked by the benzodiazepine receptor antagonist ZK 93426 and the beta-adrenoceptor antagonist propranolol. These findings suggest that FG 7142 produces a benzodiazepine-receptor mediated reduction in gastric ulcer formation, which may result from its ability to increase activity of the sympathetic nervous system.