气候变化领域集成服务门户(CCPortal): Dopaminylation of histone H3 in ventral tegmental area regulates cocaine seeking

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DOI	10.1126/science.aaw8806
	Dopaminylation of histone H3 in ventral tegmental area regulates cocaine seeking
	Lepack A.E.; Werner C.T.; Stewart A.F.; Fulton S.L.; Zhong P.; Farrelly L.A.; Smith A.C.W.; Ramakrishnan A.; Lyu Y.; Bastle R.M.; Martin J.A.; Mitra S.; O'Connor R.M.; Wang Z.-J.; Molina H.; Turecki G.; Shen L.; Yan Z.; Calipari E.S.; Dietz D.M.; Kenny P.J.; Maze I.
发表日期	2020
ISSN	0036-8075
起始页码	197
结束页码	201
卷号	368 期号:6487
英文摘要	Vulnerability to relapse during periods of attempted abstinence from cocaine use is hypothesized to result from the rewiring of brain reward circuitries, particularly ventral tegmental area (VTA) dopamine neurons. How cocaine exposures act on midbrain dopamine neurons to precipitate addiction-relevant changes in gene expression is unclear. We found that histone H3 glutamine 5 dopaminylation (H3Q5dop) plays a critical role in cocaine-induced transcriptional plasticity in the midbrain. Rats undergoing withdrawal from cocaine showed an accumulation of H3Q5dop in the VTA. By reducing H3Q5dop in the VTA during withdrawal, we reversed cocaine-mediated gene expression changes, attenuated dopamine release in the nucleus accumbens, and reduced cocaine-seeking behavior. These findings establish a neurotransmission-independent role for nuclear dopamine in relapse-related transcriptional plasticity in the VTA. © 2020 The Authors.
关键词	amidase dopamine histone H3 histone transamidase protein glutamine gamma glutamyltransferase 2 RNA unclassified drug brain cell chemical compound chemical reaction gene expression genetic analysis protein action potential amino acid substitution amino terminal sequence Article cocaine dependence controlled study dopamine release dopaminergic nerve cell dopaminergic transmission down regulation drug seeking behavior enzyme activity gene expression histone dopaminylation histone modification human human tissue hyperpolarization in vitro study motivation nerve cell plasticity nerve projection neuropathology nucleus accumbens priority journal protein expression protein function reward RNA sequence ventral tegmentum Rattus
语种	英语
来源机构	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133569
推荐引用方式 GB/T 7714	Lepack A.E.,Werner C.T.,Stewart A.F.,et al. Dopaminylation of histone H3 in ventral tegmental area regulates cocaine seeking[J]. Science,2020,368(6487).
APA	Lepack A.E..,Werner C.T..,Stewart A.F..,Fulton S.L..,Zhong P..,...&Maze I..(2020).Dopaminylation of histone H3 in ventral tegmental area regulates cocaine seeking.,368(6487).
MLA	Lepack A.E.,et al."Dopaminylation of histone H3 in ventral tegmental area regulates cocaine seeking".368.6487(2020).