title: Selective boosting of transcriptional and behavioral responses to drugs of abuse by histone deacetylase inhibition.
abstract: 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.
authors.affiliation: Area de Psicobiologia, Universitat Jaume I, Castello, Spain. csanchis@psb.uji.es
authors.forename: Carles
authors.initials: C
authors.lastname: Sanchis-Segura
authors.forename: Jose P
authors.initials: JP
authors.lastname: Lopez-Atalaya
authors.forename: Angel
authors.initials: A
authors.lastname: Barco
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D016739:Behavior, Addictive / Q000235:genetics*; D002087:Butyrates / Q000494:pharmacology; D002843:Chromatin / Q000378:metabolism; D003213:Conditioning, Psychological / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004357:Drug Synergism; D004361:Drug Tolerance; D005786:Gene Expression Regulation / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D013287:Illicit Drugs / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D013375:Substance Withdrawal Syndrome
chemical_list: D002087:Butyrates; D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D013287:Illicit Drugs