title: RACK1 affects morphine reward via BDNF.
abstract: 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.
authors: Key Laboratory of Chronobiology, Ministry of Health (Sichuan University), Sichuan University, Chengdu, PR China. bigeyes812@163.com
authors: Lihong
authors: L
authors: Wan
authors: Yizhou
authors: Y
authors: Xie
authors: Lan
authors: L
authors: Su
authors: Yanyou
authors: Y
authors: Liu
authors: Yuhui
authors: Y
authors: Wang
authors: Zhengrong
authors: Z
authors: Wang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007276:Injections, Intraventricular; D055029:Inverted Repeat Sequences; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D034741:RNA, Small Interfering; D011897:Random Allocation; D000075370:Receptors for Activated C Kinase; D012201:Reward
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009294:Narcotics; D009479:Neuropeptides; D010446:Peptide Fragments; C090294:RACK1 protein, mouse; D034741:RNA, Small Interfering; D000075370:Receptors for Activated C Kinase; D009020:Morphine