據(jù)1月8日的《科學(xué)》雜志報道說,，在一項有助于解釋藥物成癮的生物學(xué)基礎(chǔ)的小鼠研究中,，科研人員顯示了可卡因是如何影響某些與伏核中基因的開與關(guān)有關(guān)的系統(tǒng)的。
伏核是腦中“獎勵”回路中的一個關(guān)鍵性的中心,。 人們已知可卡因成癮會造成該環(huán)路中基因表達的持久性變化,，以及其適應(yīng)新環(huán)境的能力，而這些變化可能是可卡因成癮的某些行為效應(yīng)的基礎(chǔ),。
Ian Maze及其同僚在小鼠中分析了某些發(fā)生在腦神經(jīng)元染色體中的分子相互作用,，這些相互作用最終影響了不同基因的表達。 他們發(fā)現(xiàn),，長期接觸可卡因會導(dǎo)致某些形式的“組蛋白賴氨酸甲基化”的減少,，這是伏核中染色體部分的一種生物化學(xué)性修飾。 這種組蛋白賴氨酸甲基化減少可增加某些神經(jīng)元的可塑性,，使得它們變得異常容易進行相互連接,，而且還會增加小鼠對可卡因的偏好。
研究人員說,，更好地理解通過這些過程而受到調(diào)節(jié)的基因可幫助研發(fā)出更為有效的成癮性疾病的治療方法,。（生物谷Bioon.com）
更多有關(guān)上癮研究：
PNAS：一種蛋白激酶基因變異易導(dǎo)致毒品上癮
Nature：查明尼古丁上癮原因
PNAS：發(fā)現(xiàn)抑制可卡因上癮的機制
Science：可卡因上癮與人腦結(jié)構(gòu)直接相關(guān)
生物谷推薦原始出處：
Science 8 January 2010: DOI: 10.1126/science.1179438
Essential Role of the Histone Methyltransferase G9a in Cocaine-Induced Plasticity
Ian Maze,1 Herbert E. Covington, III,1 David M. Dietz,1 Quincey LaPlant,1,2 William Renthal,2 Scott J. Russo,1 Max Mechanic,2 Ezekiell Mouzon,1 Rachael L. Neve,3 Stephen J. Haggarty,4,5 Yanhua Ren,1 Srihari C. Sampath,6 Yasmin L. Hurd,1 Paul Greengard,7 Alexander Tarakhovsky,6 Anne Schaefer,7 Eric J. Nestler1,*
Cocaine-induced alterations in gene expression cause changes in neuronal morphology and behavior that may underlie cocaine addiction. In mice, we identified an essential role for histone 3 lysine 9 (H3K9) dimethylation and the lysine dimethyltransferase G9a in cocaine-induced structural and behavioral plasticity. Repeated cocaine administration reduced global levels of H3K9 dimethylation in the nucleus accumbens. This reduction in histone methylation was mediated through the repression of G9a in this brain region, which was regulated by the cocaine-induced transcription factor FosB. Using conditional mutagenesis and viral-mediated gene transfer, we found that G9a down-regulation increased the dendritic spine plasticity of nucleus accumbens neurons and enhanced the preference for cocaine, thereby establishing a crucial role for histone methylation in the long-term actions of cocaine.
1 Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA.
2 Departments of Psychiatry and Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA.
3 Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
4 Psychiatric and Neurodevelopmental Genetics Unit and Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
5 Stanley Center for Psychiatric Research, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
6 Laboratory of Lymphocyte Signaling, The Rockefeller University, New York, NY, USA.
7 Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, USA.
