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Essential role of the NO signaling pathway in the hippocampal CA1 in morphine-associated memory depends on glutaminergic receptors
| Content Provider | Semantic Scholar |
|---|---|
| Author | Shen, Fang Wang, Xue-Wei Ge, Fei-Fei Li, Yi-Jing Cui, Cai-Lian |
| Copyright Year | 2016 |
| Abstract | The nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP-dependent protein kinase (PKG) signaling pathway has been reported to play a key role in memory processing. However, little is known about its role in drug-associated reward memory. Here, we report the following. 1) The NO pathway in the CA1 is critical for the retrieval of morphine-associated reward memory. Specifically, the nNOS, sGC and PKG protein levels in the CA1 were increased after the expression of morphine conditioned place preference (CPP). Intra-CA1 injection of an NOS, sGC or PKG inhibitor prevented morphine CPP expression. 2) The involvement of the NO pathway in morphine CPP requires NR2B-containing NMDA receptors (NR2B-NMDARs). NR2B-NMDAR expression was elevated in the CA1 following morphine CPP expression, and intra-CA1 injection of the NR2B-NMDAR antagonist Ro25-6981 not only blocked morphine CPP expression but also inhibited the up-regulation of nNOS, sGC and PKG. Moreover, the Ro25-6981-induced blockade of morphine CPP was abolished by intra-CA1 injection of a NOS substrate or an sGC activator. 3) The NR2B-NMDAR stimulated the NO pathway by up-regulating the phosphorylation of Akt(Ser473). Morphine CPP expression enhanced the pAkt(Ser473) level, which has been corroborated to regulate nNOS activity, and this effect was reversed by intra-CA1 injection of Ro25-6981. 4) GluR1 acted downstream of the NO pathway. The membrane level of GluR1 in the CA1 was increased after morphine CPP expression, and this effect was prevented by pre-injection of a PKG inhibitor into the CA1. Additionally, co-immunoprecipitation revealed an interaction between PKG and GluR1; this result further indicated a role of PKG in regulating GluR1 trafficking. Collectively, the results of our study demonstrated that the activation of the NR2B-NMDAR/NO/sGC/PKG signaling pathway is necessary for the retrieval of morphine-associated reward memory. |
| Starting Page | 216 |
| Ending Page | 228 |
| Page Count | 13 |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/j.neuropharm.2015.11.008 |
| PubMed reference number | 26596557 |
| Journal | Medline |
| Volume Number | 102 |
| Alternate Webpage(s) | http://nri.bjmu.edu.cn/docs/2016-11/20161116135224241504.pdf |
| Alternate Webpage(s) | https://api.elsevier.com/content/article/pii/S0028390815301726 |
| Alternate Webpage(s) | https://www.sciencedirect.com/science/article/pii/S0028390815301726?dgcid=api_sd_search-api-endpoint |
| Alternate Webpage(s) | https://doi.org/10.1016/j.neuropharm.2015.11.008 |
| Journal | Neuropharmacology |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
