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Simvastatin Blocks Reinstatement of cocaine-induced Conditioned Place Preference in Male Mice with Brain Lipidome Remodeling

引用

Neuroscience Bulletin 2021年第12期37卷 1683-1702页

作者： Wei Xu Yuman He Jiamei Zhang Hongchun Li Xuemei Wan Menglu Li Yonghai Wang Rui Xu Haoluo Zhang Yanping Dai Haxiaoyu Liu Linhong Jiang Ying Zhao Xiaobo Cen National Chengdu Center for Safety Evaluation of Drugs State Key Laboratory of Biotherapy and Collaborative Innovation Center for BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Sichuan Center for Disease Control and Prevention Chengdu 610041China Shenzhen Key Laboratory of Drug Addiction the Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsShenzhen 518055China School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University)Ministry of EducationCollaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of ShandongYantai UniversityYantai 264005China

Drug-associated reward memories are conducive to intense craving and often trigger *** has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is ***,we used a mass spectrometry-based lipidomic method to evaluate the impact of simvastatin on the mouse brain in a cocaine-induced reinstatement *** found that simvastatin blocked the reinstatement of cocaine-induced conditioned place preference(CPP)without affecting CPP ***,only simvastatin administered during extinction prevented cocaine-primed *** lipidome analysis showed that the nucleus accumbens was the region with the greatest degree of change caused by *** metabolism of fatty-acids,phospholipids,and triacylglycerol was profoundly *** reversed most of the effects on phospholipids induced by *** correlation matrix showed that cocaine and simvastatin significantly reshaped the lipid metabolic pathways in specific brain ***,simvastatin almost reversed all changes in the fatty acyl profile and unsaturation caused by *** summary,pre-extinction treatment with simvastatin facilitates cocaine extinction and prevents cocaine relapse with brain lipidome remodeling.

关键词： Simvastatin cocaine relapse Extinction Lipidome Conditioned place preference

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