目的探讨特麦角脲治疗海洛因依赖的作用机制。方法成年雄性SD大鼠,随机分为正常对照组、海洛因依赖形成期生理盐水干预组、海洛因依赖形成期特麦角脲干预组、复发期生理盐水干预组和复发期特麦角脲干预组;除正常对照组外,其余4组分别建立海洛因静脉自身给药和线索诱发复发模型,干预后灌注固定,留取各脑区切片,采用免疫组化和原位杂交技术,分别检测各脑区多巴胺D2受体蛋白和mRNA、强啡肽原蛋白、前强啡肽原mRNA表达水平。结果伏核多巴胺D2受体蛋白在海洛因依赖形成期表达下调,在复发期表达上升,多巴胺D2受体基因表达与蛋白表达基本一致,特麦角脲可使复发期受体蛋白表达回降。杏仁核中央核多巴胺D2受体蛋白和基因表达在复发期上调,特麦角脲可使基因表达回降。前额叶多巴胺D2受体蛋白和基因表达在形成期上调,蛋白表达在复发期下调,特麦角脲使复发期基因表达下调。伏核强啡肽蛋白和基因在复发期表达上调,特麦角脲使之回降。杏仁核中央核强啡肽蛋白在复发期表达上调,特麦角脲使之回降。结论海洛因依赖形成期中脑边缘系统多巴胺活动升高,复发期活动降低,特麦角脲对此有双向调节作用。复发期强啡肽活动上升,特麦角脲可使之降低,有治疗海洛因滥用的潜力。 Objective To investigate the mechanism of heroin dependent treatment with terguride. Methods Adult male Sprague-Dawley rats were randomly divided into three groups: normal control group, normal saline group during heroin dependence formation phase, terguride intervention group during heroin dependence phase, normal saline intervention group during relapse and terguride recurrent phase. Control group, the other four groups were established self-administration of heroin vein and clues-induced relapse model, perfusion fixation after intervention, the brain sections were taken, immunohistochemistry and in situ hybridization were used to detect dopamine D2 Body protein and mRNA, dynorphin, pro-dynorphin mRNA expression levels. Results The expression of dopamine D2 receptor protein in nucleus accumbens was down-regulated in heroin dependence stage and increased in relapse stage. The expression of dopamine D2 receptor gene was basically consistent with that of protein. Terguride decreased the expression of receptor protein in relapse stage. Adenocarcinoma central nucleus dopamine D2 receptor protein and gene expression in the relapse phase, terguride can gene expression down. Prefrontal dopamine D2 receptor protein and gene expression in the formation of up-regulation, protein expression in the recurrence down regulation, terguride the recurrence of gene expression down. Nucleocapsid-dynorphin protein and gene expression was up-regulated during the relapse phase, with terguride decreasing. Central nucleolar dynorphin protein in the amygdala is upregulated in the relapse phase, and terguride causes it to fall back. Conclusions Dopamine activity in the midbrain system is increased in heroin dependence and decreased in the relapse phase, and terguride has bidirectional regulation on it. Increased activity of dynorphin during relapse, with reduced doses of terguride, has the potential to treat heroin abuse.