3 years ago

Phosphorylated SNAP25 in the CA1 regulates morphine-associated contextual memory retrieval via increasing GluN2B-NMDAR surface localization

Phosphorylated SNAP25 in the CA1 regulates morphine-associated contextual memory retrieval via increasing GluN2B-NMDAR surface localization
Yan Liu, Yijing Li, Meng Jia, Xiaowei Sun, Cailian Cui, Na Wang, Xinjuan Wang
Although our previous studies have demonstrated both protein kinase C (PKC) and GluN2B-containing N-methyl-d-aspartate receptor (GluN2B-NMDAR) play crucial roles in morphine-associated learning and memory, the relationship between them remains unexplored. In this study, we validated the enhanced PKC and membrane GluN2B protein expression in the hippocampal CA1 after morphine conditioned place preference (CPP) expression in rats. Interestingly, we also found that phosphorylation of SNAP25 at Ser187 (pSer187-SNAP25), a PKC-activated target, was significantly increased following morphine CPP expression. Blocking the pSer187-SNAP25 by intra-CA1 injection of an interfering peptide impaired morphine CPP expression and accompanied by the reduced ratio of GluN2B membrane/total in the CA1. In addition, intra-CA1 blockade of pSer187-SNAP25 did not affect natural learning and memory process as evidenced by intact sucrose-induced CPP expression and normal locomotor activity in rats. Therefore, our results reveal that enhanced pSer187-SNAP25 by PKC recruits GluN2B-NMDAR to the membrane surface in the hippocampal CA1 and mediates context-induced addiction memory retrieval. Our findings in this study fill in the missing link and provide better understanding of the molecular mechanisms involved in morphine-associated contextual memory retrieval. Protein kinase C (PKC), pSer187-SNAP25 and GluN2B was critical to morphine conditioned place preference (CPP) expression in the CA1. TAT-S187 peptide in the CA1 impaired morphine CPP expression and decreased the GluN2B surface localization. PKC interacted with pS187-SNAP25 accompanied by increasing GluN2B surface localization in the CA1 after morphine CPP expression.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/adb.12558

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