Institutional Repository of Key Laboratory of Mental Health, CAS
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([email protected]) |
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 |
DOI | 10.1016/j.biopsych.2017.12.008 |
发表期刊 | BIOLOGICAL PSYCHIATRY |
ISSN | 0006-3223 |
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 |
引用统计 | |
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 |
推荐引用方式 GB/T 7714 | 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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文件名称/大小 | 文献类型 | 版本类型 | 开放类型 | 使用许可 | ||
2017 BP Role of Dors(730KB) | 期刊论文 | 作者接受稿 | 限制开放 | CC BY-NC-SA | 请求全文 |
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