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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
第一作者Li, Xuan
2018
发表期刊Biological psychiatry
ISSN0006-3223
文章类型Article
期号17页码:32314-4
Q分类Q1
产权排序3
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
DOI10.1016/j.biopsych.2017.12.008
收录类别SCI
语种英语
引用统计
被引频次:1[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.National Institute on Drug Abuse, National Institutes of Health
2.University of Texas Southwestern Medical Center
3.Institute of Psychology, Chinese Academy of Sciences
4.College of Medicine, Hanyang University
5.Medical University of South Carolina
6.Icahn School of Medicine at Mount Sinai
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(17):32314-4.
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(17),32314-4.
MLA Li, Xuan,et al."Role of Dorsal Striatum Histone Deacetylase 5 in Incubation of Methamphetamine Craving".Biological psychiatry .17(2018):32314-4.
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