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mGluR 5 in the nucleus accumbens shell regulates morphine‐associated contextual memory through reactive oxygen species signaling
Author(s) -
Qi Chong,
Wang Xinjuan,
Ge Feifei,
Li Yijing,
Shen Fang,
Wang Junkai,
Cui Cailian
Publication year - 2015
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12222
Subject(s) - metabotropic glutamate receptor , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 5 , pharmacology , nucleus accumbens , morphine , chemistry , mapk/erk pathway , conditioned place preference , agonist , neuroscience , microbiology and biotechnology , signal transduction , psychology , medicine , biology , receptor , biochemistry
Emerging evidence indicates that metabotropic glutamate receptor 5 ( mGluR 5) critically modulates drug and drug‐related behaviors. However, the role of mGluR 5 in the opiate‐induced contextual memory remains unclear. Here, we found that microinfusion of the mGluR 5 antagonist 3‐((2‐Methyl‐1,3‐thiazol‐4‐yl)ethynyl)pyridine ( MTEP ) into the nucleus accumbens ( NAc ) shell, but not into the core, significantly attenuated the expression of morphine conditioned place preference ( CPP ) in rats. Following the expression of morphine CPP , the protein level of membrane mGluR 5 was selectively increased in the NAc shell. In primary striatal neurons, we observed that treatment with the mGluR 5 agonist CHPG increased the phosphorylation level of extracellular signal‐regulated kinase ( ERK ), which was dependent on the mGluR 5‐inositol‐1,4,5‐trisphosphate‐reactive oxygen species ( ROS ) pathway. Moreover, the microinjection of the ROS scavenger Tempol into the NAc shell of rats blocked the expression of morphine CPP . Further, the administration of t‐ BOOH , a ROS donor, into the NAc shell rescued the retrieval impairment of morphine CPP produced by MTEP . Our previous study demonstrated that the expression of morphine CPP increased the phosphorylation of ERK selectively in the NAc shell. Thus, results of the present study suggest that mGluR 5 in the NAc shell, but not in the core, is essential for the retrieval of morphine contextual memory, which is mediated at least in part, through the ROS / ERK signaling pathway. Uncovering the molecular basis of opiate contextual memory will benefit the development of new therapeutic approaches for the treatment of opiate addiction.