Chromatin Remodeling Is a Key Mechanism Underlying Cocaine-Induced Plasticity in Striatum

Department of Psychiatry and Center for Basic Neuroscience, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
Neuron (Impact Factor: 15.05). 11/2005; 48(2):303-14. DOI: 10.1016/j.neuron.2005.09.023
Source: PubMed


Given that cocaine induces neuroadaptations through regulation of gene expression, we investigated whether chromatin remodeling at specific gene promoters may be a key mechanism. We show that cocaine induces specific histone modifications at different gene promoters in striatum, a major neural substrate for cocaine's behavioral effects. At the cFos promoter, H4 hyperacetylation is seen within 30 min of a single cocaine injection, whereas no histone modifications were seen with chronic cocaine, consistent with cocaine's ability to induce cFos acutely, but not chronically. In contrast, at the BDNF and Cdk5 promoters, genes that are induced by chronic, but not acute, cocaine, H3 hyperacetylation was observed with chronic cocaine only. DeltaFosB, a cocaine-induced transcription factor, appears to mediate this regulation of the Cdk5 gene. Furthermore, modulating histone deacetylase activity alters locomotor and rewarding responses to cocaine. Thus, chromatin remodeling is an important regulatory mechanism underlying cocaine-induced neural and behavioral plasticity.

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Available from: David W Self, Jun 18, 2014
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    • "Another hypothesis is that NaB could induce a reduction of HAT levels, as already shown in human cells (Covault et al. 1982). However, we cannot yet rule out a possible effect of HDACi on non-epigenetic mechanisms, such as deacetylation of transcription factors and non-histone proteins, as suggested by other published data (Davie 2003; Kumar et al. 2005; Kalda et al. 2007). Altogether, our study demonstrated that administration of the HDACi NaB inhibits several ethanol addictionrelated behaviors using different and complementary procedures. "
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