Peripheral and central effects of atropine and chlorpromazine on gastric motility and ulceration in stressed rats.

Abstract

In rats exposed to restraint and water immersion stress, inhibitory effects of atropine (ATR) and chlorpromazine (CPZ) on stress-induced gastric ulceration and motility were studied to clarify which of central and peripheral origins was responsible for these effects. The drug dose ratio of peripheral (intravenous, i.v.) route versus central (intracerebroventricular, i.c.v.) route required to produce an approx. 50% inhibition of gastric ulceration or motility was estimated. Gastric ulceration was prevented by pretreatment with each drug via either route, and there was no great difference in the dose ratio of each drug (i.v.:i.c.v. = 4:1) for the inhibition. The stress-enhanced gastric motility was immediately depressed by each drug via either route. This inhibitory effect of CPZ was short-lasting as compared with that of ATR, and the complete blockade was observed after administration of i.v. ATR or i.c.v. CPZ at higher doses. The ATR dose ratio for this inhibition was less than 10, while the CPZ dose ratio was from 10 to 25. The treatment with CPZ, but not with ATR, caused a definite change in EEG patterns, along with a decrease in body temperature or heart rate. The effect of pretreatment with ATR or CPZ on gastric motility during stress was also investigated. Only the administration of ATR, via either route, appreciably inhibited the gastric motility. Thus, it was suggested that: (1) the inhibitory effect of ATR on gastric motility may be of peripheral rather than central origin, while that of CPZ predominantly of central origin; (2) the anti-ulcerogenic effect of ATR and CPZ may be predominantly of peripheral origin, and the mechanisms involved in ATR may be associated with inhibition of gastric motility, which is different from those in CPZ.