l-THP对氯胺酮依赖大鼠不同阶段条件位置偏爱的影响及DA作用机制研究  

Effects of l-tetrahydropalmatine on different stages of conditioned place preference in ketamine dependent rats and the mechanism of DA

作　　者：杜艳 高杏翠[2] 苏红亮 王玉瑾 杜丽[4] 贠克明 Du Yan;Gao Xingcui;Su Hongliang;Wang Yujin;Du Li;Yun Keming(China Research institute of Radiation Protection,Taijuan Shanxi 030006;School of Pharmaceutical Science,Shanxi Medical University,Taiyuan,Shanxi,030001;School of Forensic Medicine,Shanxi Medical University,Taiyuan,Shanxi,030001;The Tumor Hospital of Shanxi Province,Taiyuan,Shanxi,030013)

机构地区：[1]中国辐射防护研究院,山西太原030006 [2]山西医科大学药学院,山西太原030001 [3]山西医科大学法医学院,山西太原030001 [4]山西省肿瘤医院,山西太原030013

出　　处：《中国法医学杂志》2024年第1期50-54,共5页Chinese Journal of Forensic Medicine

基　　金：山西省自然基金面上项目(20210302123302);山西医科大学博士启动基金(BS201732)。

摘　　要：目的考察l-四氢巴马汀(l-THP)对氯胺酮诱导大鼠条件位置偏爱(CPP)的表达、消退和复吸的影响。检测大鼠大脑纹状体(CPu)多巴胺(DA)在不同时间点的含量。方法采用CPP建立氯胺酮成瘾大鼠模型,以CPP得分为指标,考察l-THP对氯胺酮诱导大鼠CPP的表达、消退和复吸的影响。采用超高速液相色谱-串联质谱(UPLC-MS/MS)技术测定氯胺酮给药以及l-THP干预后30 min、60 min、90 min、120 min、150 min大鼠CPu的DA含量。结果l-THP可减弱氯胺酮诱导大鼠CPP的表达,并促进其消退,抑制氯胺酮的复吸。此外,l-THP联合氯胺酮给药可显著抑制氯胺酮诱导的大鼠CPu中DA含量的增加。结论l-THP抑制氯胺酮奖赏作用的机制可能与阻滞DA受体,减少DA神经递质释放有关。l-THP对于治疗氯胺酮成瘾具有潜在的意义。Objective To observe the effects of Levo-tetrahydropalmatine(l-THP)on the expression,regression and relapse of conditioned place preference(CPP)in ketamine induced rats,and to detect the content of dopamine(DA)in the striatum(caudate putamen,CPu)of the rat brain at different time points.Methods Ketamine addiction rat model was established by CPP.The effects of l-THP on the expression,regression and relapse of ketamine induced rat CPP were investigated using CPP score as the index.The content of DA in CPu of rats was determined by ultra-performance liquid chromatography coupled to tandem mass spectrometry(UPLC-MS/MS)after ketamine administration and l-THP intervention at 30 min,60 min,90 min,120 min and 150 min.Results It indicated that l-THP could decrease the expression of CPP in ketamine induced rats,promote the process of CPP resolution and inhibit the process of relapse.In addition,l-THP combined with ketamine administration significantly inhibited the ketamine-induced increase in DA content in the CPu of the rats.Conclusion The mechanism of l-THP inhibiting the reward effect of ketamine may be related to blocking DA receptors and reducing the release of DA neurotransmitters.l-THP has potential implications for the treatment of ketamine addiction.

关 键 词：L-四氢巴马汀 氯胺酮 条件位置偏爱 多巴胺 UPLC-MS/MS 

分 类 号：D918.93[政治法律—法学]