左旋延胡索乙素对吗啡条件性位置偏爱大鼠伏核NR1蛋白表达的影响

The effect of l-tetrahydropalmatine on NR1 protein expression of NAc in morphine-induced Conditioned Place Preference rats

目的研究左旋延胡索乙素(l-tetrahydropalmatine,l-THP)对吗啡诱发条件性位置偏爱(conditioned place preference,CPP)大鼠伏核(nucleus accumbens,NAc)中N-甲基-D-天冬氨酸受体NR1亚基(NR1)表达改变的影响。方法大鼠随机分组,即正常对照组、模型CPP组、生理盐水治疗组及l-THP低(0.94 mg/kg)、中(1.88 mg/kg)和高(3.76 mg/kg)治疗组。正常对照组皮下注射等量生理盐水外,剩余各组大鼠采用颈背部皮下剂量递增法注射吗啡(起始剂量10 mg/kg,每天递增10 mg/kg,至注射10 d时为100 mg/kg),经CPP训练10 d,末次训练后48 h进行CPP检测确认CPP模型成功。各治疗组大鼠灌胃给药,每天1次,连续治疗6 d后进行CPP检测,之后处死大鼠并采用脑立体定位仪取大鼠NAc脑组织,利用Western Blot方法检测NR1基因的蛋白表达。结果经CCP检测,模型组大鼠在白箱(吗啡伴药箱)停留时间,与生理盐水组比较明显延长(P<0.05),而经l-THP 1.88和3.76 mg/kg治疗后,停留时间恢复至正常对照组水平。Western Blot检测到CPP大鼠NAc核团NR1的蛋白表达较正常对照组显著增加(P<0.01),l-THP 1.88和3.76 mg/kg治疗后,NR1蛋白表达被逆转。结论在大鼠吗啡精神依赖过程中l-THP可显著抑制NAc核团中NR1蛋白表达的增加,这一作用可能是l-THP加速大鼠吗啡CPP效应消退的机制之一。

Objective To observe the change on expression of the N- methyl- D- aspartate receptor NR1 subunit（ NR1） in nucleus accumbens（ NAc） of the morphine induced Conditioned Place Preference（ CPP） rat after the treatment with l- tetrahydropalmatine（ l- THP）. Methods Sixty rats were randomly divided into normal NS group,morphine induced Conditionned Place Preference（ CPP） model group,normal NS treatment group and three dosages of l- THP treatment groups. The rats were trained in black compartments and white ones（ drug-paired compartment） with the increasing doses of morphine for 10 days（ hypodermically injected from 10 to 100 mg / kg）. Models of CPP were validated in those psychological dependence rats after 48 h training. The high,medium and low dosage group of l- THP were given l- THP 0. 76,1. 88 and 0. 94 mg / kg lavage treatment,respectively. NS treatment group were lavaged normal saline for 6 days and they were killed after test of CPP.Western blotting detected the expression changes of NR1 protein. Results Compared with NS control group,the residence time in the white box（ morphine pair box） of CPP model group rats was significantly longer（ P〈 0. 01）. After the treatment of l- THP（ 3. 76,1. 88 and 0. 94 mg / kg）,residence time return to that of normal saline control group. Compared with the NS control group,the expression levels of NR1 was increased in NAc in CPP group,but NR1 of l- THP（ 3. 76 and 1. 88 mg / kg） reduced in NAc（ P〈 0. 01）. Conclusion The l-THP could reverse the NR1 protein expression in NAc of the morphine psychological dependence rats,might be the potential mechanism of pharmacological effects which should accelerate the fading process of morphine CPP effects in the experimented bodies.