The Role Of 5-HT Involved In The Mechanism Of Preventing Chemotherapy-induced Nausea And Vomiting Of Forsythia Suspensain In Rat Pica Model

Objective:To study the role of 5-hydroxytryptamine(5-HT) involved in the mechanism of preventing Chemotherapy-induced nausea and vomiting of Forsythia suspensa in rat pica model. Methods:Emetic stimuli induced kaoli ingestion behavior (pica behavior) in rats (i.e., species that do not have the emetic reflex) is analogous to nausea and emesis.The pica behavior is served as an index of nausea and vomiting. We successfully established a cisplatin-induced pica model in rats. A HPLC-fluorescence detection method was developed for the determination of 5-HT and 5-HIAA in serum and brain of rats.5-HT and 5-HT3A receptor immunoreactive cells in rats' brain and intestine were investigated by the method of immunohistochemical technique. Results:(1) Forsythia suspensa-low, Forsythia suspensa-median, Forsythia suspensa-high dose and Forsythin significantly decreased the kaolin consumption at acute vomiting in rats (0-24h post-cisplatin injection), of which only Forsythia suspensa-high dose decreased the kaolin consumption at delayed vomiting in rats (24-48 and 48-72h post-cisplatin injection). (2)Compared with the model group, Forsythia suspensa-low, Forsythia suspensa-median and Forsythia suspensa-high doses can reduce 5-HT and 5-HIAA content in rats'brain in the trend, but there were no statistical difference between them. (3)Forsythia suspensa-low, Forsythia suspensa-median, Forsythia suspensa-high dose and Forsythin were associated with a decrease in the concentration of 5-HT3A receptor in rats' brainstem, the effects are better than ondansetron. Forsythia suspensa-high dose was associated with a decrease in the concentration of 5-HT in rats' intestine. Forsythia suspensa-median, Forsythia suspensa-high dose were associated with a decrease in the concentration of 5-HT3A receptor expression in rats'intestine.Conclusion:Forsythia suspensa showed an antiemetic effect at acute and delayed nausea and vomiting in rat pica model. The mechanism may be the inhibitions of 5-HT,5-HT3A receptor in the brainstem and intestine. Forsythin is effective for the acute vomiting, and the mechanism may be related to 5-HT and 5-HT3A receptor.