美沙酮是治疗阿片类药物成瘾最有效药物之一，但仍不能完全解决复吸问题。复吸根源在于患者的精神依赖。文献和本课题组研究表明，延胡索可显著改善阿片类药物的精神依赖，Netrin-1/DCC信号通路可调控精神依赖的关键多巴胺环路VTA-mPFC-NAc。基于此，假设延胡索、美沙酮联合治疗可减少复吸，机制是延胡索调节VTA-mPFC-NAc多巴胺神经环路中的Netrin-1/DCC信号通路。本课题拟采用吗啡诱导的条件性位置偏爱方法建立延胡索、美沙酮联合治疗模型。通过检测条件性位置偏爱的消退和VTA-mPFC-NAc环路中Netrin-1/DCC表达及神经元形态变化，验证延胡索、美沙酮联合治疗阿片类药物精神依赖的效果。通过特异性干预VTA-mPFC-NAc多巴胺神经环路及环路内Netrin-1/DCC信号通路，验证延胡索治疗阿片类药物精神依赖的神经生物学机制，为防治阿片类药物复吸提供生物学基础。

Methadone is one of the most effective drugs for the treatment of opioid addiction, but it still cannot prevent relapse completely. The root cause of relapse is mental dependence on opioids. The literature and our previous research showed that yanhusuo can significantly improve the mental dependence of opioids. Netrin-1/DCC signaling pathway can regulate the VTA-mPFC-NAc circuit that critical in mental dependence. Based on this, we propose the hypothesis that the combination therapy of yanhusuo and methadone could reduce relapse, and the mechanism may be the Netrin-1/DCC signaling pathway in the VTA-mPFC-NAc dopamine circuit. In this study, we would use the morphine-induced conditioned place preference to establish yanhusuo and methadone combination therapy model. By examining the subside of conditioned positional preference, and the Netrin-1/DCC expression and neuronal morphology in the VTA-mPFC-NAc circuit, we would verify the effect of combination therapy of yanhusuo and methadone. By specifically intervening the VTA-mPFC-NAc dopamine circuit and the Netrin-1/DCC signaling pathway in this circuit, the neurobiological mechanism of yanhusuo treatment for mental dependence of opioids would be verified. Our task would provide a biological basis for the prevention and treatment of opioid relapse.