GluN2亚基在海洛因诱导CPP模型大鼠PrL区的表达

目的:研究大鼠内侧前额叶皮质(mPFC)边缘前区(PrL)GluN2亚基在海洛因诱导条件位置性偏爱(CPP)及戒断状态的表达。方法:24只SD大鼠随机分为对照组(control)和海洛因诱导组。海洛因诱导组大鼠按实验进程分为两种状态,即海洛因诱导CPP状态(heroin)和海洛因戒断状态(withdrawal)。用小剂量递增法皮下注射海洛因,行大鼠海洛因诱导CPP建模,并自然戒断,免疫荧光染色检测各组大鼠PrL区GluN2亚基NR2A、NR2B、NR2C、NR2D的表达。结果:大鼠经过连续7 d小剂量递增法注射海洛因,形成了稳定的CPP;免疫荧光染色结果显示,大鼠CPP状态PrL区NR2B表达较对照组显著增强(P<0.01),其他亚基无明显变化。海洛因自然戒断7 d后,戒断状态大鼠PrL区NR2A、NR2C表达较对照组和CPP状态皆显著增强(P<0.01)。戒断状态NR2B表达水平显著高于对照组(P<0.01),但与CPP状态无显著差异。结论:大鼠海洛因依赖CPP的形成与PrL区NR2B亚基的活性密切相关,NR2A和NR2C可能参与药物戒断症状的调控。推测PrL区GluN2不同亚基在海洛因成瘾不同阶段作用不同,并可能成为临床海洛因成瘾干预和治疗的重要靶点。

The expression of GluN2 subunits in Pr L region of heroin-induced CPP rats

Objective:To investigate the expression of GluN2 subunits in the prelimbic(PrL)of medial prefrontal cortex(mPFC)during heroin-induced CPP and withdrawal.Methods:Twenty four SD rats were randomly divided into control group and heroin induced group.The heroin induced group rats were divided into two states,including heroin induced CPP status and heroin withdrawal status.The model of CPP induced by heroin in rats was established by lowdose incremental heroin subcutaneous injection,then withdrawal naturally.The expression of GluN2 subunits NR2A,NR2B,NR2C and NR2D in the PrL region of each group of rats was detected by immunofluorescence staining.Results:After 7 days of low-dose incremental heroin injection,the CPP model was established successfully;The results of immunofluorescence staining showed that the expression of NR2B in the PrL region during CPP was significantly enhanced compared with that control group(P<0.01),while there was no significant change in other subunits.After 7 days of heroin naturally withdrawal,the expression of NR2A and NR2C in the PrL region of withdrawal rats were both significantly enhanced than control group and CPP status(P<0.01).The expression of NR2B in withdrawal status is significantly higher than that of control group(P<0.01),but similar to the CPP status.Conclusion:It suggested that the formation of heroin-induced CPP in rats maybe related to the activity of NR2B subunit in PrL region,and the subunits of NR2A and NR2C are possibly involved in the regulation of heroin withdrawal symptoms.Therefore,we speculate that different subunits of GluN2 in PrL region play unequal roles in heroin addiction,and may be an important target for clinical heroin addiction intervention and treatment.