伏核壳部含有GluN2B亚基的NMDA受体参与吗啡奖赏记忆的再巩固

GLUN2B-CONTAINING NMDA RECEPTORS IN THE SHELL OF THE NUCLEUS ACCUMBENS WERE INVOLVED IN THE RECONSOLIDATION OF MORPHINE-INDUCED REWARD MEMORY

目的:再次暴露于药物相关线索能唤起药物成瘾记忆并使之处于不稳定状态,此时可经再巩固后形成稳定记忆,也可干扰其再巩固过程削弱或消除该记忆。本研究检测了伏核内含有GluN2B亚基的NMDA受体在吗啡奖赏记忆再巩固中的作用。方法:将已形成吗啡条件性位置偏爱(conditioned place preference,CPP)的大鼠再次暴露于伴吗啡箱后,观察其伏核壳部和核心部NMDA受体各亚基的蛋白水平;再次暴露于伴吗啡箱后,在大鼠双侧伏核壳部和核心部分别注射GluN2B亚基选择性NMDA受体拮抗剂Ro 25-6981,观察对大鼠吗啡CPP表达的影响。结果:(1)吗啡CPP大鼠再次暴露于用药环境后,伏核壳部NMDA受体的GluN2B亚基蛋白水平特异性升高,Glu N2A亚基降低,Glu N1亚基不变;核心部GluN2B、Glu N2A和Glu N1亚基蛋白水平均无明显变化。(2)再次暴露于用药环境后,伏核壳部注射Ro 25-6981的大鼠没有表现出对伴吗啡箱的偏爱,这种对吗啡CPP的抑制作用可持续至给药后14 d,并且小剂量吗啡处理不能使CPP行为重建;核心部注射Ro 25-6981的大鼠仍可表现出对伴吗啡箱的偏爱。结论:伏核壳部含有GluN2B亚基的NMDA受体在吗啡奖赏记忆再巩固中发挥了重要的作用。

Objective： Re -exposure to the drug- related cues can reactivate the drug- associated memory and trigger the relapse of drug abuse. If the reconsolidation of drug - related memory is interrupted, the relapse may be prevented. This study is designed to determine the role of GluN2B - containing NMDARs in the nucleus accumbens （Nac） on the reconsolidation of morphine - induced reward memory. Methods ： Using the conditioned place preference （CPP） as an animal model that mimics drug- associated learning and memory, the protein level of GluN2B, GluN2A and GluN1 subunits were detected in the Nac shell and core after re - exposure to the drug - paired context. The effect of Ro 25 - 6981, an antagonist of GluN2B - containing NMDARs, on the reconsolidation of morphine CPP in rats was investigated. Resuhs：GluN2B subunits protein level was increased while the GluN2A subunits weredecreased in the Nac shell after re - exposure to drug - paired context. Protein level of GluN1 subunits in the Nac shell and these three kinds of NMDAR subunits in the Nac core stayed unchanged. After re - exposure to drug- paired context, microinjection of Ro 25 -6981 into the Nac shell but not the core could inhibit the expression of morphine CPP. This effect lasted for at least 14 days and was not abolished by a priming injection of morphine. Conclusion：These results suggested that the GluN2B - NMDARs in the Nac shell play a critical role in the reconsolidation of morphine - induced reward memory.