Research article summary (published 12 May 2009):

Genome-wide analysis of chromatin regulation by cocaine reveals a role for sirtuins.

Full Abstract

Changes in gene expression contribute to the long-lasting regulation of the brain's reward circuitry seen in drug addiction; however, the specific genes regulated and the transcriptional mechanisms underlying such regulation remain poorly understood. Here, we used chromatin immunoprecipitation coupled with promoter microarray analysis to characterize genome-wide chromatin changes in the mouse nucleus accumbens, a crucial brain reward region, after repeated cocaine administration. Our findings reveal several interesting principles of gene regulation by cocaine and of the role of DeltaFosB and CREB, two prominent cocaine-induced transcription factors, in this brain region. The findings also provide comprehensive insight into the molecular pathways regulated by cocaine-including a new role for sirtuins (Sirt1 and Sirt2)-which are induced in the nucleus accumbens by cocaine and, in turn, dramatically enhance the behavioral effects of the drug.

Author information

Author/s: Renthal, William (W); Kumar, Arvind (A); Xiao, Guanghua (G); Wilkinson, Matthew (M); Covington, Herbert E (HE); Maze, Ian (I); Sikder, Devanjan (D); Robison, Alfred J (AJ); LaPlant, Quincey (Q); Dietz, David M (DM); Russo, Scott J (SJ); Vialou, Vincent (V); Chakravarty, Sumana (S); Kodadek, Thomas J (TJ); Stack, Ashley (A); Kabbaj, Mohamed (M); Nestler, Eric J (EJ);

Affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Neuron (Neuron), published in United States. (Language: eng)

Reference: 2009-May; vol 62 (issue 3) : pp 335-48

Dates: Created 2009/05/18; Completed 2009/06/23;

PMID: 19447090, status: MEDLINE (last retrieval date: 6/23/2009, IMS Date: 23 Jun 2009 00:00:00)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Chromatin - drug effects Cocaine - pharmacology Cyclic AMP Response Element-Binding Protein - drug effects; metabolism Dopamine Uptake Inhibitors - pharmacology Feedback, Biochemical - drug effects Gene Expression Regulation - drug effects Genome-Wide Association Study Male

Mice Mice, Inbred C57BL Nucleus Accumbens - drug effects; metabolism Oligonucleotide Array Sequence Analysis Promoter Regions, Genetic - drug effects; physiology Proto-Oncogene Proteins c-fos - drug effects; metabolism Reinforcement (Psychology) Signal Transduction - drug effects Sirtuins - drug effects; metabolism

Associated Chemicals: Chromatin (0) ; Cyclic AMP Response Element-Binding Protein (0) ; Dopamine Uptake Inhibitors (0) ; Fosb protein, mouse (0) ; Proto-Oncogene Proteins c-fos (0) ; Cocaine (50-36-2) ; Sirtuins (EC 3.5.1.-)

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