AIM: To investigate the role of excitatory amino acid transporter 3( EAAT3 ) in prefrontal cortex and hippocampus in morphine relapse by detecting the changes of EAAT3 expression in prefrontal cortex and hippocampus in conditioned place preference ( CPP ) reinstatement rat model induced by morphine.METHODS: Forty adult male SD rats, weighing 200 -250 g, were randomly divided into 5 groups with 8 rats each: control group, CPP establishment group ( Es ), CPP extinction group ( Ex ), reinstatement 2 h group ( Re2 ) and reinstatement 4 h group ( Re4 ).Intraperitoneal ( ip ) injection of morphine was applied at a constant dose ( 10 mg/kg ) for 10 days to the established CPP model.Normal saline instead of morphine was used to induce CPP extinction for 10 days.CPP was reinstated following a single priming injection of morphine ( 2.5 mg/kg ).After the CPP behavior test, the rats were sacrificed, and the prefrontal cortex and hippocampus were collected for detecting the levels of EAAT3 by Western blotting.RESULTS: The accumulated time the rats spent in the drug - paired chamber was significantly longer in Es group, Re2 group and Re4 group than that in control group ( P ＜0.05 ).Compared with control group, the expression of EAAT3 in prefrontal cortex significantly decreased both in Es group and Re4 group ( P ＜ 0.05 ).No significant change of EAAT3 in hippocampus among groups was observed ( P ＞ 0.05 ), while EAAT3 in hippocampal CA1 area significantly increased in Es group and Ex group as compared with control group ( P ＜0.05 ).CONCLUSION: The expression of EAAT3 in prefrontal cortex decreases both in CPP establishment and reinstatement models, indicating that down - regulation of EAAT3 in prefrontal cortex may partly participate in the formation of opium relapse.%目的:观察吗啡诱导的条件性位置偏爱(CPP)复燃大鼠前额叶皮层和海马区兴奋性氨基酸转运蛋白3(EAAT3)的表达变化,探讨前脑皮层及海马区EAAT3在阿片类药物复吸过程中的作用.方法:成年雄性SD大鼠40只,随机分为对照组(control)、CPP建立(Es)、消退(Ex)、复燃2 h(Re2)、复燃4 h(Re4)组,每组8只.腹腔注射吗啡(10 mg/kg)连续10 d,建立CPP模型;停止给药使CPP逐渐消退;单次腹腔注射吗啡 2.5 mg/kg诱导已消退的CPP复燃.Western blotting检测各组大鼠前额叶皮层和海马区EAAT3蛋白表达变化.结果:(1)腹腔注射恒定剂量的吗啡10 mg/kg,Es组大鼠在伴药箱的停留时间比control组明显延长(P<0.05),成功建立CPP模型;待CPP消退后,吗啡2.5 mg/kg腹腔注射诱发Re2和Re4组大鼠在伴药箱的停留时间再次比control组明显延长(P<0.05),CPP复燃.(2)Es组前额叶皮层EAAT3比control组表达减少(P<0.05),CPP消退的Ex组表达回升,在Re4组表达再次减少(P<0.05).(3)海马区EAAT3在各组表达水平未见明显变化(P>0.05);而Es、Ex组海马CA1区EAAT3比control组表达明显升高(P<0.05).结论:吗啡诱导CPP复燃时,前额叶皮层EAAT3的蛋白表达水平降低,重现CPP建立时的变化,提示阿片类药物复吸行为的形成可能与前脑皮层EAAT3的表达减少有关.
展开▼
