Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum

Arvind Kumar, Kwang Ho Choi, William Renthal, Nadia M. Tsankova, David E H Theobald, Hoang Trang Truong, Scott J. Russo, Quincey LaPlant, Teresa S. Sasaki, Kimberly N. Whistler, Rachael L. Neve, David W. Self, Eric J. Nestler

Research output: Contribution to journalArticle

573 Scopus citations

Abstract

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. ΔFosB, 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.

Original languageEnglish (US)
Pages (from-to)303-314
Number of pages12
JournalNeuron
Volume48
Issue number2
DOIs
StatePublished - Oct 20 2005

ASJC Scopus subject areas

  • Neuroscience(all)

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    Kumar, A., Choi, K. H., Renthal, W., Tsankova, N. M., Theobald, D. E. H., Truong, H. T., Russo, S. J., LaPlant, Q., Sasaki, T. S., Whistler, K. N., Neve, R. L., Self, D. W., & Nestler, E. J. (2005). Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum. Neuron, 48(2), 303-314. https://doi.org/10.1016/j.neuron.2005.09.023