Induction of histone acetylation in the nucleus accumbens (NAc), a key brain reward region, promotes cocaine-induced alterations in gene expression. Histone deacetylases (HDACs) tightly regulate the acetylation of histone tails, but little is known about the functional specificity of different HDAC isoforms in the development and maintenance of cocaine-induced plasticity, and previous studies of HDAC inhibitors report conflicting effects on cocaine-elicited behavioral adaptations. Here we demonstrate that specific and prolonged blockade of HDAC1 in NAc of mice increased global levels of histone acetylation, but also induced repressive histone methylation and antagonized cocaine-induced changes in behavior, an effect mediated in part through a chromatin-mediated suppression of GABAA receptor subunit expression and inhibitory tone on NAc neurons. Our findings suggest a new mechanism by which prolonged and selective HDAC inhibition can alter behavioral and molecular adaptations to cocaine and inform the development of therapeutics for cocaine addiction.
Pubmed ID: 23475113 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
View all literature mentionsSoftware tool that detects peaks of any type, any shape, any direction, and any size for neuroscientists who are studying spontaneous activities. Allows detection of virtually any kind of peaks including spontaneous miniature synaptic currents and potentials, action potential spikes, calcium imaging peaks, amperometric peaks, ECG peaks etc. It includes the complex and multiple peak detection algorithm. Has post-detection analyses including essential plots and statistical parameters. Group Analysis provides specialized and detailed analysis options for action potentials, decay fitting, fEPSP/population spikes, amperometry, etc.
View all literature mentionsSoftware tool that detects peaks of any type, any shape, any direction, and any size for neuroscientists who are studying spontaneous activities. Allows detection of virtually any kind of peaks including spontaneous miniature synaptic currents and potentials, action potential spikes, calcium imaging peaks, amperometric peaks, ECG peaks etc. It includes the complex and multiple peak detection algorithm. Has post-detection analyses including essential plots and statistical parameters. Group Analysis provides specialized and detailed analysis options for action potentials, decay fitting, fEPSP/population spikes, amperometry, etc.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentions