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

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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

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Chromatin Assembly and Disassembly
Cocaine
Histone Code
Genes
Neuronal Plasticity
Histone Deacetylases
Brain-Derived Neurotrophic Factor
Gene Expression Regulation
Locomotion
Transcription Factors

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kumar, A., Choi, K. H., Renthal, W., Tsankova, N. M., Theobald, D. E. H., Truong, H. T., ... 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

Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum. / Kumar, Arvind; Choi, Kwang Ho; Renthal, William; Tsankova, Nadia M.; Theobald, David E H; Truong, Hoang Trang; Russo, Scott J.; LaPlant, Quincey; Sasaki, Teresa S.; Whistler, Kimberly N.; Neve, Rachael L.; Self, David W.; Nestler, Eric J.

In: Neuron, Vol. 48, No. 2, 20.10.2005, p. 303-314.

Research output: Contribution to journalArticle

Kumar, A, Choi, KH, Renthal, W, Tsankova, NM, Theobald, DEH, Truong, HT, Russo, SJ, LaPlant, Q, Sasaki, TS, Whistler, KN, Neve, RL, Self, DW & Nestler, EJ 2005, 'Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum', Neuron, vol. 48, no. 2, pp. 303-314. https://doi.org/10.1016/j.neuron.2005.09.023
Kumar A, Choi KH, Renthal W, Tsankova NM, Theobald DEH, Truong HT et al. Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum. Neuron. 2005 Oct 20;48(2):303-314. https://doi.org/10.1016/j.neuron.2005.09.023
Kumar, Arvind ; Choi, Kwang Ho ; Renthal, William ; Tsankova, Nadia M. ; Theobald, David E H ; Truong, Hoang Trang ; Russo, Scott J. ; LaPlant, Quincey ; Sasaki, Teresa S. ; Whistler, Kimberly N. ; Neve, Rachael L. ; Self, David W. ; Nestler, Eric J. / Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum. In: Neuron. 2005 ; Vol. 48, No. 2. pp. 303-314.
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