title: RACK1 promotes maintenance of morphine-associated memory via activation of an ERK-CREB dependent pathway in hippocampus.
abstract: Existence of long-term drug-associated memories may be a crucial factor in drug cravings and relapse. RACK1 plays a critical role in morphine-induced reward. In the present study, we used conditioned place preference (CPP) to assess the acquisition and maintenance of morphine conditioned place preference memory. The hippocampal protein level of RACK1 and synaptic quantitation were evaluated by Western blotting, immunohistochemistry and electron microscopy, respectively. Additionally, shRACK1 (shGnb2l1) was used to silence RACK1 in vivo to evaluate the role and the underlying mechanism of RACK1 in maintenance of morphine CPP memory. We found that morphine induced CPP was maintained for at least 7 days after the last morphine treatment, which indicated a positive correlation with hippocampal RACK1 level, and was accompanied simultaneously by increases in the synapse density and hippocampal expression of synaptophysin (SYP), phosphorylation of extracellular signal-regulated kinase1/2 (pERK1/2) and the phosphorylation of cyclic adenosine monophosphate response element-binding (pCREB). ShGnb2l1 icv injection significantly suppressed the expression of all above proteins, decreased the synapse density in the hippocampus and attenuated the acquisition and maintenance of morphine CPP. Our present study highlights that RACK1 plays an important role in the maintenance of morphine CPP, likely via activation of ERK-CREB pathway in hippocampus.
authors.affiliation: Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.|Sichuan University "985 project - Science and Technology Innovation Platform for Novel Drug Development", Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Litao
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.|Sichuan University "985 project - Science and Technology Innovation Platform for Novel Drug Development", Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Jiejun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.|Sichuan University "985 project - Science and Technology Innovation Platform for Novel Drug Development", Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Liming
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.|Sichuan University "985 project - Science and Technology Innovation Platform for Novel Drug Development", Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Wan
mesh_terms: D000818:Animals; D003216:Conditioning, Operant; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D007276:Injections, Intraventricular; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009473:Neuronal Plasticity / Q000187:drug effects; D009479:Neuropeptides / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism; D012201:Reward; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009479:Neuropeptides; C090294:RACK1 protein, mouse; D034741:RNA, Small Interfering; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D009020:Morphine
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