PMID- 21885037 OWN - NLM STAT- MEDLINE DCOM- 20120127 LR - 20171116 IS - 1872-6240 (Electronic) IS - 0006-8993 (Linking) VI - 1416 DP - 2011 Oct 6 TI - RACK1 affects morphine reward via BDNF. PG - 26-34 LID - 10.1016/j.brainres.2011.07.045 [doi] AB - Chronic morphine addiction may trigger functional changes in the mesolimbic dopamine system, which is believed to be the neurobiological substrate of opiate addiction. Brain derived neurotrophic factor (BDNF) has been implicated in addiction-related pathology in animal studies. Our previous studies have shown that RACK1 is involved in morphine reward in mice. The recent research indicates nuclear RACK1 by localizing at the promoter IV region of the BDNF gene and the subsequent chromatin modifications leads to the activation of the promoter and transcription of BDNF. The present study was designed to investigate if shRACK1 (a short hairpin RNA of RACK1) could reverse the mice's behavioral responses to morphine and BDNF expression in hippocampus and prefrontal cortex. No significant changes were observed in vehicle-infused mice which received no morphine treatment (CONC) and shRACK1-infused mice which received no morphine treatment (CONR), whereas vehicle-infused mice preceded the morphine injection (MIC) showed increased BDNF expression in hippocampus and prefrontal cortex, as compared to vehicle-infused mice which received no morphine treatment (CONC). Intracerebroventricular shRACK1 treatment reversed these, and in fact, ShRACK1-infused mice preceded the morphine injection (MIR) showed reduced BDNF expression in hippocampus and prefrontal cortex, as compared to MIC. In the conditioned place preference (CPP) test, inactivating RACK1 markedly reduces morphine-induced conditioned place preference. Non-specific changes in CPP could not account for these effects since general CPP of shRACK1- and vehicle-infused animals was not different. Combined behavioral and molecular approaches have support the possibility that the RACK1-BDNF system plays an important role in the response to morphine-induced reward. CI - Copyright (c) 2011 Elsevier B.V. All rights reserved. FAU - Wan, Lihong AU - Wan L AD - Key Laboratory of Chronobiology, Ministry of Health (Sichuan University), Sichuan University, Chengdu, PR China. bigeyes812@163.com FAU - Xie, Yizhou AU - Xie Y FAU - Su, Lan AU - Su L FAU - Liu, Yanyou AU - Liu Y FAU - Wang, Yuhui AU - Wang Y FAU - Wang, Zhengrong AU - Wang Z LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110728 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Narcotics) RN - 0 (Neuropeptides) RN - 0 (Peptide Fragments) RN - 0 (RACK1 protein, mouse) RN - 0 (RNA, Small Interfering) RN - 0 (Receptors for Activated C Kinase) RN - 76I7G6D29C (Morphine) SB - IM MH - Analysis of Variance MH - Animals MH - Association Learning/drug effects/*physiology MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Gene Expression Regulation/*physiology MH - Hippocampus/drug effects/*metabolism MH - Injections, Intraventricular MH - Inverted Repeat Sequences MH - Male MH - Mice MH - Mice, Inbred ICR MH - Morphine/pharmacology MH - Narcotics/pharmacology MH - Neuropeptides/genetics/*metabolism MH - Peptide Fragments MH - Prefrontal Cortex/drug effects/*metabolism MH - RNA, Small Interfering MH - Random Allocation MH - Receptors for Activated C Kinase MH - Reward EDAT- 2011/09/03 06:00 MHDA- 2012/01/28 06:00 CRDT- 2011/09/03 06:00 PHST- 2011/06/09 00:00 [received] PHST- 2011/07/21 00:00 [revised] PHST- 2011/07/22 00:00 [accepted] PHST- 2011/09/03 06:00 [entrez] PHST- 2011/09/03 06:00 [pubmed] PHST- 2012/01/28 06:00 [medline] AID - S0006-8993(11)01373-4 [pii] AID - 10.1016/j.brainres.2011.07.045 [doi] PST - ppublish SO - Brain Res. 2011 Oct 6;1416:26-34. doi: 10.1016/j.brainres.2011.07.045. Epub 2011 Jul 28.