目的 建立模仿临床情景发生的反安慰剂恶心效应的大鼠实验模型.方法 通过硝酸甘油和舒马曲坦注射建立偏头痛大鼠治疗模型,使用氯化锂作为恶心诱导剂,并将其与糖精溶液配对;采取观察学习和条件反射双重机制诱发反安慰剂恶心;通过动物行为学、免疫荧光、实时定量聚合酶链式反应等技术进行模型验证.结果 在诱导日接受生理盐水注射的大鼠表现出显著的恶心行为和条件性味觉回避,并伴有延髓5-羟色胺、大麻素信号通路以及孤束核的激活.结论 本研究成功开发新的反安慰剂恶心动物实验模型,有助于反安慰剂效应神经生物学分子机制的研究.
Objective To establish a rat experimental model that mimics the nocebo nausea effect occur-ring in clinical scenarios.Methods A therapeutic model of migraine in rats was established by injecting nitro-glycerine and sumatriptan.Lithium chloride was used as a nausea inducer and paired with saccharin solutions.A dual mechanism of observational learning and conditioned reflexes was adopted to induce nocebo nausea,and the model was validated by animal behavioral,immunofluorescence,and real-time quantitative polymerase chain reaction(RT-qPCR)techniques.Results Rats receiving saline injections on the induction day exhibited significant nausea behavior and conditioned taste avoidance with activation of the medullary 5-hydroxytryptamine(5-HT)and cannabinoid signaling pathways as well as the nucleus of the solitary tract.Conclusion This study successfully developed a new animal experimental model of nocebo nausea,which con-tributes to the study of the molecular mechanism of the neurobiology of the nocebo effect.