吗啡精神依赖大鼠奖赏环路多巴胺递质含量和D2受体表达的变化

目的：观察吗啡条件性位置偏爱（cPP）大鼠中脑腹侧被盖区-伏核-前额叶皮质（VTA—NAc—PFC）奖赏环路3个脑区多巴胺（DA）递质和多巴胺2受体（D2受体）的同步变化，从神经递质和受体层面探讨该环路中多巴胺能系统的阿片类精神依赖机制。方法：SD大鼠随机分为模型组和生理盐水组，吗啡剂量递增注射建立大鼠吗啡cPP模型；高效液相色谱法测定各脑区DA含量；免疫组化和Westernblot技术检测D2受体的表达。结果：模型组大鼠伴药箱停留时间增加；vTA、NAc、PFC的DA递质升高、D2受体平均吸光度值和平均光密度值均降低，同Ns组比较，差异有统计学意义（均P〈0．05）。结论：奖赏环路3个脑区多巴胺递质的增加和D2受体表达下调的同步改变，与吗啡精神依赖的形成具有一定的相关性。

CHANGES OF DOPAMINE CONTENT AND D2 RECEPTOR EXPRESSION IN REWARD CIRCUIT IN MORPHINE- DEPENDENT RATS

Objective： To investigate the mechanism of psychological dependence of morphine, the synchronous changes of dopamine and D2 receptor were observed in reward circuit （ VTA - NAc - PFC） of rats with morphine - induced conditioned place preference （CPP） and it could provide experimental data for mutiple targets of the new detoxification drug from a new perspective of network pharmacology. Methods：The SD rats were randomly divided into two groups：model group（M） and saline group（ N ）. The rat CPP model was established by injecting the rats with an increasing dosage of morphine. The DA contents in VTA, NAc and PFC were detected by HLPC, and the expression levels of D2 receptor in samples were tested by immunohistochemistry and Western blot. Results：Compared with the saline group, rats in model group spent more time in morphine - paired box and produced higher content of dopamine in VTA, NAc and PFC, and the levels of D2 receptor in VTA, NAc and PFC were decreased in the average optical density and the integral, optical density. These differences were significant（P 〈 O. 05）. Conclusion：There were synchronous changes between the increased content of dopamine and the decreased level of D2 receptor in reward circuit of morphine dependent rats and it is linked to the psychological dependence of morphine.