Nomura K, Maeda N, Kuratani K, Yamaguchi I
Tsukuba Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan.
Jpn J Pharmacol. 1995 May;68(1):33-9. doi: 10.1254/jjp.68.33.
Gastric lesions were developed in the communication box paradigm (CB) in mice as well as in the activity-stress paradigm (AS) in rats. Treatment with sulpiride (10-320 mg/kg, p.o.) attenuated these psychological stress-induced gastric lesions in a dose-dependent manner, while it failed to suppress those induced by physical stress such as restraint water-immersion (WI) and indomethacin treatment (IND). In contrast, treatment with famotidine (0.32-10 mg/kg, p.o.) dose-dependently attenuated the gastric lesions induced by physical stress but not those by psychological stress. Pylorus-ligation study revealed that famotidine strongly reduced gastric acid secretion, whereas sulpiride minimally affected that. It was also demonstrated that physical stress (WI) enhanced acid secretion while psychological stress (CB and AS) rather depressed that. These results suggest that the mechanisms of gastric lesion formation are clearly different between physical and psychological stress and that sulpiride specifically attenuates psychological stress lesions possibly through a central mechanism.
在小鼠的社交箱范式(CB)以及大鼠的活动应激范式(AS)中均会出现胃部病变。舒必利(10 - 320毫克/千克,口服)治疗以剂量依赖的方式减轻了这些心理应激诱导的胃部病变,而它未能抑制由诸如束缚水浸(WI)和吲哚美辛治疗(IND)等物理应激诱导的胃部病变。相比之下,法莫替丁(0.32 - 10毫克/千克,口服)治疗以剂量依赖的方式减轻了由物理应激诱导的胃部病变,但对心理应激诱导的胃部病变无效。幽门结扎研究表明,法莫替丁强烈减少胃酸分泌,而舒必利对胃酸分泌影响极小。还证明了物理应激(WI)会增强胃酸分泌,而心理应激(CB和AS)则会抑制胃酸分泌。这些结果表明,物理应激和心理应激导致胃部病变形成的机制明显不同,舒必利可能通过中枢机制特异性减轻心理应激性病变。