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Aim: Evodiamine (EVO) has been reported to play an important role in regulating gastrointestinal motility, but the evidence is insufficient, and the mechanism remains unknown. The aim of this study is to investigate the possible role of EVO in stress-induced colonic hypermotility and the potential mechanisms via both in vivo and in vitro investigations., Methods: Male Sprague-Dawley rats were exposed to water avoidance stress (WAS) for 1 h or sham WAS daily for 10 consecutive days to construct the rat model. The colonic contractile activity was studied in an organ bath system. The serum CCK-8 level was detected using an enzyme immunoassay kit, and gastrointestinal transit was detected by intragastric administration of India ink., Results: WAS induced gastrointestinal hypermotility in male rats. EVO significantly inhibited the contractile activity of colonic muscle strips; this effect was not blocked by TTX and the CCK 1 receptor antagonist devazepide. Chronic WAS induced a slight but nonsignificant increase in the serum CCK-8 level, while EVO elevated the serum CCK-8 level in the WAS rats in a dose-dependent manner. Exogenous CCK-8 significantly inhibited the contractile activity of the colonic muscle strips; this effect was not blocked by TTX but was completely blocked by devazepide. Both EVO and CCK-8 inhibited gastrointestinal transit, and the effect of EVO could be partially blocked by devazepide., Significance: EVO can reverse stress-induced gastrointestinal hypermotility. This effect may partially occur as a result of promoting the release of CCK and then activating the CCK 1 receptor instead of directly activating the CCK 1 receptor., (Copyright © 2018 Elsevier Inc. All rights reserved.)