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Role of Dorsal Striatum Histone Deacetylase 5 in Incubation of Methamphetamine Craving
Li, Xuan1; Carreria, Maria B.2; Witonsky, Kailyn R.1; Zeric, Tamara1; Lofaro, Olivia M.1; Bossert, Jennifer M.1; Zhang, Jianjun3; Surjono, Felicia1; Richie, Christopher T.1; Harvey, Brandon K.1; Son, Hyeon4; Cowan, Christopher W.5; Nestler, Eric J.6; Shaham, Yavin1
通讯作者Li, Xuan(annali@umd.edu)
摘要BACKGROUND: Methamphetamine (meth) seeking progressively increases after withdrawal (incubation of meth craving). We previously demonstrated an association between histone deacetylase 5 (HDAC5) gene expression in the rat dorsal striatum and incubation of meth craving. Here we used viral constructs to study the causal role of dorsal striatum HDAC5 in this incubation. METHODS: In experiment 1 (overexpression), we injected an adeno-associated virus bilaterally into dorsal striatum to express either green fluorescent protein (control) or a mutant form of HDAC5, which strongly localized to the nucleus. After training rats to self-administer meth (10 days, 9 hours/day), we tested the rats for relapse to meth seeking on withdrawal days 2 and 30. In experiment 2 (knockdown), we injected an adeno-associated virus bilaterally into the dorsal striatum to express a short hairpin RNA either against luciferase (control) or against HDAC5. After training rats to self-administer meth, we tested the rats for relapse on withdrawal days 2 and 30. We also measured gene expression of other HDACs and potential HDAC5 downstream targets. RESULTS: We found that HDAC5 overexpression in dorsal striatum increased meth seeking on withdrawal day 30 but not day 2. In contrast, HDAC5 knockdown in the dorsal striatum decreased meth seeking on withdrawal day 30 but not on day 2; this manipulation also altered other HDACs (Hdac1 and Hdac4) and potential HDAC5 targets (Gnb4 and Suv39h1). CONCLUSIONS: Results demonstrate a novel role of dorsal striatum HDAC5 in incubation of meth craving. These findings also set up future work to identify HDAC5 targets that mediate this incubation.
关键词Dorsal striatum Epigenetics HDAC5 Incubation Methamphetamine Relapse
2018-08-01
语种英语
DOI10.1016/j.biopsych.2017.12.008
发表期刊BIOLOGICAL PSYCHIATRY
ISSN0006-3223
卷号84期号:3页码:213-222
收录类别SCI
资助项目National Institute on Drug Abuse Intramural Research Program ; National Institute on Drug Abuse[P01 DA008227] ; National Institute on Drug Abuse[R01 DA032708] ; National Institutes of Health[F31 DA035073] ; China Scholarship Council[201604910135] ; National Research Foundation of Korea Grant - Ministry of Education, Science and Technology, Republic of Korea[2016R1A2B2006474]
出版者ELSEVIER SCIENCE INC
WOS关键词COCAINE-SEEKING BEHAVIOR ; CONTEXT-INDUCED REINSTATEMENT ; MEDIAL PREFRONTAL CORTEX ; TIME-DEPENDENT CHANGES ; NEUROTROPHIC FACTOR TRANSCRIPTION ; INHIBITOR SODIUM-BUTYRATE ; VENTRAL TEGMENTAL AREA ; NUCLEUS-ACCUMBENS ; DORSOLATERAL STRIATUM ; DNA METHYLATION
WOS研究方向Neurosciences & Neurology ; Psychiatry
WOS类目Neurosciences ; Psychiatry
WOS记录号WOS:000438895700009
资助机构National Institute on Drug Abuse Intramural Research Program ; National Institute on Drug Abuse ; National Institutes of Health ; China Scholarship Council ; National Research Foundation of Korea Grant - Ministry of Education, Science and Technology, Republic of Korea
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被引频次:30[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/25708
专题中国科学院心理健康重点实验室
通讯作者Li, Xuan
作者单位1.NIDA, Intramural Res Program, NIH, US Dept HHS, Baltimore, MD USA
2.Univ Texas Southwestern Med Ctr Dallas, Neurosci Grad Program, Dallas, TX 75390 USA
3.Chinese Acad Sci, Inst Psychol, CAS Key Lab Mental Hlth, Beijing, Peoples R China
4.Hanyang Univ, Coll Med, Dept Biochem & Mol Biol, Seoul, South Korea
5.Med Univ South Carolina, Dept Neurosci, Charleston, SC USA
6.Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA
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Li, Xuan,Carreria, Maria B.,Witonsky, Kailyn R.,et al. Role of Dorsal Striatum Histone Deacetylase 5 in Incubation of Methamphetamine Craving[J]. BIOLOGICAL PSYCHIATRY,2018,84(3):213-222.
APA Li, Xuan.,Carreria, Maria B..,Witonsky, Kailyn R..,Zeric, Tamara.,Lofaro, Olivia M..,...&Shaham, Yavin.(2018).Role of Dorsal Striatum Histone Deacetylase 5 in Incubation of Methamphetamine Craving.BIOLOGICAL PSYCHIATRY,84(3),213-222.
MLA Li, Xuan,et al."Role of Dorsal Striatum Histone Deacetylase 5 in Incubation of Methamphetamine Craving".BIOLOGICAL PSYCHIATRY 84.3(2018):213-222.
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