Journal
NEUROPSYCHOPHARMACOLOGY
Volume 34, Issue 13, Pages 2642-2654Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2009.125
Keywords
addiction; neuroplasticity; histone modification; sensitization; morphine; gene expression
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Funding
- European Commission [MEXT-CT-2003-509550]
- Spanish Ministry of Science and Innovation [SAF2008-00611, CSD2007-00023]
- Fundacion Ramon Areces and Fundacio la Marato de TV3
- Conselleria d'Educacio de la Generalitat Valenciana [GV/2007/098]
- Ministry of Science and Innovation
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Histone acetylation and other modifications of the chromatin are important regulators of gene expression and, consequently, may contribute to drug-induced behaviors and neuroplasticity. Earlier studies have shown that a reduction in histone deacetylase (HDAC) activity results in the enhancement of some psychostimulant-induced behaviors. In this study, we extend those seminal findings by showing that the administration of the HDAC inhibitor sodium butyrate enhances morphine-induced locomotor sensitization and conditioned place preference. In contrast, this compound has no effects on the development of morphine tolerance and dependence. Similar effects were observed for cocaine and ethanol-induced behaviors. These behavioral changes were accompanied by a selective boosting of a component of the transcriptional program activated by chronic morphine administration that included circadian clock genes and other genes relevant to addictive behavior. Our results support a specific function for histone acetylation and the epigenetic modulation of transcription at a reduced number of biologically relevant loci on non-homeostatic, long-lasting, drug-induced behavioral plasticity. Neuropsychopharmacology (2009) 34, 2642-2654; doi:10.1038/npp.2009.125; published online 2 September 2009
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