Selective boosting of transcriptional and behavioral responses to drugs of abuse by histone deacetylase inhibition.
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.
Sanchis-Segura
Carles
C
Area de Psicobiologia, Universitat Jaume I, Castello, Spain. csanchis@psb.uji.es
Lopez-Atalaya
Jose P
JP
Barco
Angel
A
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
D002087:Butyrates; D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D013287:Illicit Drugs