Extinction of Aversive Memories Associated with Morphine Withdrawal Requires ERK-Mediated Epigenetic Regulation of Brain-Derived Neurotrophic Factor Transcription in the Rat Ventromedial Prefrontal Cortex

doi:10.1523/JNEUROSCI.1991-12.2012

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第二研究室

	Extinction of Aversive Memories Associated with Morphine Withdrawal Requires ERK-Mediated Epigenetic Regulation of Brain-Derived Neurotrophic Factor Transcription in the Rat Ventromedial Prefrontal Cortex
	Wang, Wei-Sheng 1; Kang, Shuo 1; Liu, Wen-Tao 2; Li, Mu 1; Liu, Yao 1; Yu, Chuan 1; Chen, Jie 1; Chi, Zhi-Qiang1 ; He, Ling 2; Liu, Jing-Gen1
刊名	JOURNAL OF NEUROSCIENCE
	2012-10-03
卷号	32 期号:40 页码:13763-13775
ISSN号	0270-6474
DOI	10.1523/JNEUROSCI.1991-12.2012
文献子类	Article
英文摘要	Recent evidence suggests that histone deacetylase (HDAC) inhibitors facilitate extinction of rewarding memory of drug taking. However, little is known about the role of chromatin modification in the extinction of aversive memory of drug withdrawal. In this study, we used conditioned place aversion (CPA), a highly sensitive model for measuring aversive memory of drug withdrawal, to investigate the role of epigenetic regulation of brain-derived neurotrophic factor (BDNF) gene expression in extinction of aversive memory. We found that CPA extinction training induced an increase in recruiting cAMP response element-binding protein (CREB) to and acetylation of histone H3 at the promoters of BDNF exon I transcript and increased BDNF mRNA and protein expression in the ventromedial prefrontal cortex (vmPFC) of acute morphine-dependent rats and that such epigenetic regulation of BDNF gene transcription could be facilitated or diminished by intra-vmPFC infusion of HDAC inhibitor trichostatin A or extracellular signal-regulated kinase (ERK) inhibitor U0126 (1,4-diamino-2,3-dicyano-1,4-bis(methylthio) butadiene) before extinction training. Correspondingly, disruption of the epigenetic regulation of BDNF gene transcription with U0126 or suppression of BDNF signaling with Trk receptor antagonist K252a or BDNF scavenger tyrosine kinase receptor B (TrkB)-Fc blocked extinction of CPA behavior. We also found that extinction training-induced activation of ERK and CREB and extinction of CPA behavior could be potentiated or suppressed by intra-vmPFC infusion of D-cycloserine, a NMDA receptor partial agonist or aminophosphonopentanoic acid, a NMDA receptor antagonist. We conclude that extinction of aversive memory of morphine withdrawal requires epigenetic regulation of BDNF gene transcription in the vmPFC through activation of the ERK-CREB signaling pathway perhaps in a NMDA receptor-dependent manner.
资助项目	Ministry of Science and Technology of China[2009CB522005] ; Ministry of Science and Technology of China[2012ZX09301001-005] ; Ministry of Science and Technology of China[2008BAI49B05] ; Foundation of National Natural Science of China[81130087]
WOS关键词	ACTIVATED PROTEIN-KINASE ; CONDITIONED PLACE PREFERENCE ; FEAR-POTENTIATED STARTLE ; VENTRAL TEGMENTAL AREA ; LONG-TERM POTENTIATION ; GYRUS GRANULE NEURONS ; C-FOS INDUCTION ; NUCLEUS-ACCUMBENS ; COCAINE-SEEKING ; D-CYCLOSERINE
WOS研究方向	Neurosciences & Neurology
语种	英语
出版者	SOC NEUROSCIENCE
WOS记录号	WOS:000309506600013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277913]
专题	药理学第二研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Liu, Jing-Gen
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.China Pharmaceut Univ, Dept Pharmacol, Nanjing 210009, Peoples R China
推荐引用方式 GB/T 7714	Wang, Wei-Sheng,Kang, Shuo,Liu, Wen-Tao,et al. Extinction of Aversive Memories Associated with Morphine Withdrawal Requires ERK-Mediated Epigenetic Regulation of Brain-Derived Neurotrophic Factor Transcription in the Rat Ventromedial Prefrontal Cortex[J]. JOURNAL OF NEUROSCIENCE,2012,32(40):13763-13775.
APA	Wang, Wei-Sheng.,Kang, Shuo.,Liu, Wen-Tao.,Li, Mu.,Liu, Yao.,...&Liu, Jing-Gen.(2012).Extinction of Aversive Memories Associated with Morphine Withdrawal Requires ERK-Mediated Epigenetic Regulation of Brain-Derived Neurotrophic Factor Transcription in the Rat Ventromedial Prefrontal Cortex.JOURNAL OF NEUROSCIENCE,32(40),13763-13775.
MLA	Wang, Wei-Sheng,et al."Extinction of Aversive Memories Associated with Morphine Withdrawal Requires ERK-Mediated Epigenetic Regulation of Brain-Derived Neurotrophic Factor Transcription in the Rat Ventromedial Prefrontal Cortex".JOURNAL OF NEUROSCIENCE 32.40(2012):13763-13775.