title: Persistent variations in neuronal DNA methylation following cocaine self-administration and protracted abstinence in mice.
abstract: Continued vulnerability to relapse during abstinence is characteristic of cocaine addiction and suggests that drug-induced neuroadaptations persist during abstinence. However, the precise cellular and molecular attributes of these adaptations remain equivocal. One possibility is that cocaine self-administration leads to enduring changes in DNA methylation. To address this possibility, we isolated neurons from medial prefrontal cortex and performed high throughput DNA sequencing to examine changes in DNA methylation following cocaine self-administration. Twenty-nine genomic regions became persistently differentially methylated during cocaine self-administration, and an additional 28 regions became selectively differentially methylated during abstinence. Altered DNA methylation was associated with isoform-specific changes in the expression of co-localizing genes. These results provide the first neuron-specific, genome-wide profile of changes in DNA methylation induced by cocaine self-administration and protracted abstinence. Moreover, our findings suggest that altered DNA methylation facilitates long-term behavioral adaptation in a manner that extends beyond the perpetuation of altered transcriptional states.
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, Australia 4072.
authors.forename: Danay
authors.initials: D
authors.lastname: Baker-Andresen
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, Australia 4072.
authors.forename: Qiongyi
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, Australia 4072; Center for the Neurobiology of Learning and Memory and Department of Neurobiology and Behavior, University of California, Irvine, CA, 92617.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia 3052; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK CB2 2QQ.
authors.forename: Bianca
authors.initials: B
authors.lastname: Jupp
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia 3052.
authors.forename: Rose
authors.initials: R
authors.lastname: Chesworth
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia 3052.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lawrence
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, Australia 4072; Center for the Neurobiology of Learning and Memory and Department of Neurobiology and Behavior, University of California, Irvine, CA, 92617.
authors.forename: Timothy
authors.initials: T
authors.lastname: Bredy
keywords: DNA methylation; MBD; cocaine self-administration; genome-wide; neuron; next-generation sequencing; relapse