{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T08:27:42Z","timestamp":1787905662876,"version":"build-2784847793"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T00:00:00Z","timestamp":1652659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Substance abuse and addiction represent a significant public health problem that impacts multiple dimensions of society, including healthcare, the economy, and the workforce. In 2021, over 100,000 drug overdose deaths were reported in the US, with an alarming increase in fatalities related to opioids and psychostimulants. Understanding the fundamental gene regulatory mechanisms underlying addiction and related behaviors could facilitate more effective treatments. To explore how repeated drug exposure alters gene regulatory networks in the brain, we combined capped small (cs)RNA-seq, which accurately captures nascent-like initiating transcripts from total RNA, with Hi-C and single nuclei (sn)ATAC-seq. We profiled initiating transcripts in two addiction-related brain regions, the prefrontal cortex (PFC) and the nucleus accumbens (NAc), from rats that were never exposed to drugs or were subjected to prolonged abstinence after oxycodone or cocaine intravenous self-administration (IVSA). Interrogating over 100,000 active transcription start regions (TSRs) revealed that most TSRs had hallmarks of bonafide enhancers and highlighted the KLF\/SP1, RFX, and AP1 transcription factors families as central to establishing brain-specific gene regulatory programs. Analysis of rats with addiction-like behaviors versus controls identified addiction-associated repression of transcription at regulatory enhancers recognized by nuclear receptor subfamily 3 group C (NR3C) factors, including glucocorticoid receptors. Cell-type deconvolution analysis using snATAC-seq uncovered a potential role of glial cells in driving the gene regulatory programs associated with addiction-related phenotypes. These findings highlight the power of advanced transcriptomics methods to provide insight into how addiction perturbs gene regulatory programs in the brain.<\/jats:p>","DOI":"10.3389\/fnins.2022.858427","type":"journal-article","created":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T05:18:38Z","timestamp":1652678318000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Glucocorticoid Receptor-Regulated Enhancers Play a Central Role in the Gene Regulatory Networks Underlying Drug Addiction"],"prefix":"10.3389","volume":"16","author":[{"given":"Sascha H.","family":"Duttke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Montilla-Perez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max W.","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hairi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieselot L. G.","family":"Carrette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giordano de","family":"Guglielmo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"George","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham A.","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Benner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Telese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4174","DOI":"10.1158\/0008-5472.CAN-20-4010","article-title":"Implications of enhancer transcription and ernas in cancer.","volume":"81","author":"Adhikary","year":"2021","journal-title":"Cancer Res."},{"key":"B2","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1126\/science.282.5387.298","article-title":"Transition from moderate to excessive drug intake: change in hedonic set point.","volume":"282","author":"Ahmed","year":"1998","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1038\/nn872","article-title":"Neurobiological evidence for hedonic allostasis associated with escalating cocaine use.","volume":"5","author":"Ahmed","year":"2002","journal-title":"Nat. Neurosci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/S0893-133X(99)00133-5","article-title":"Persistent increase in the motivation to take heroin in rats with a history of drug escalation.","volume":"22","author":"Ahmed","year":"2000","journal-title":"Neuropsychopharmacology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1038\/nn.2282","article-title":"Stress and addiction: glucocorticoid receptor in dopaminoceptive neurons facilitates cocaine seeking.","volume":"12","author":"Ambroggi","year":"2009","journal-title":"Nat. Neurosci."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1126\/science.1234167","article-title":"A switch between topological domains underlies HoxD genes collinearity in mouse limbs.","volume":"340","author":"Andrey","year":"2013","journal-title":"Science"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2019.00377","article-title":"Diversity and emerging roles of enhancer RNA in regulation of gene expression and cell fate.","volume":"7","author":"Arnold","year":"2019","journal-title":"Front Cell Dev. Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"3619","DOI":"10.1016\/j.celrep.2018.08.080","article-title":"Single-cell RNA-Seq uncovers a robust transcriptional response to morphine by glia.","volume":"24","author":"Avey","year":"2018","journal-title":"Cell Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"11435","DOI":"10.1073\/pnas.172091899","article-title":"CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli.","volume":"99","author":"Barrot","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B10","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1101\/sqb.2015.80.027268","article-title":"Regulatory domains and their mechanisms.","volume":"80","author":"Benabdallah","year":"2015","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevE.83.036103","article-title":"Fast unfolding of communities in large networks.","volume":"2008","author":"Blondel","year":"2008","journal-title":"J. Stat. Mech."},{"key":"B12","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.cell.2019.09.004","article-title":"Genomic decoding of neuronal depolarization by stimulus-specific npas4 heterodimers.","volume":"179","author":"Brigidi","year":"2019","journal-title":"Cell"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/ejn.15226","article-title":"Hippocampal glucocorticoid target genes associated with enhancement of memory consolidation.","author":"Buurstede","year":"2021","journal-title":"Eur. J. Neurosci."},{"key":"B14","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1126\/science.282.5397.2272","article-title":"Regulation of cocaine reward by CREB.","volume":"282","author":"Carlezon","year":"1998","journal-title":"Science"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14331-y","article-title":"Nr4a1 suppresses cocaine-induced behavior via epigenetic regulation of homeostatic target genes.","volume":"11","author":"Carpenter","year":"2020","journal-title":"Nat. Commun."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1111\/j.1530-0277.2007.00397.x","article-title":"Identification of candidate genes for alcohol preference by expression profiling of congenic rat strains.","volume":"31","author":"Carr","year":"2007","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1523\/ENEURO.0033-21.2021","article-title":"The cocaine and oxycodone biobanks, two repositories from genetically diverse and behaviorally characterized rats for the study of addiction.","volume":"8","author":"Carrette","year":"2021","journal-title":"eNeuro"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/genes10010043","article-title":"Genomic enhancers in brain health and disease.","volume":"10","author":"Carullo","year":"2019","journal-title":"Genes (Basel)"},{"key":"B19","doi-asserted-by":"crossref","DOI":"10.1126\/science.aav1898","article-title":"The chromatin accessibility landscape of primary human cancers","volume":"362","author":"Corces","year":"2018","journal-title":"Science"},{"key":"B20","doi-asserted-by":"publisher","first-page":"7927","DOI":"10.1523\/JNEUROSCI.0548-15.2015","article-title":"Opposing role for Egr3 in nucleus accumbens cell subtypes in cocaine action.","volume":"35","author":"Chandra","year":"2015","journal-title":"J. Neurosci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/nature12024","article-title":"Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking.","volume":"496","author":"Chen","year":"2013","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1097\/00001756-200004270-00017","article-title":"Association of the N-acetyltransferase I gene (NATI) with mild and severe substance abuse.","volume":"11","author":"Comings","year":"2000","journal-title":"Neuroreport"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2019.00292","article-title":"Dopamine d3 receptor antagonism reverses the escalation of oxycodone self-administration and decreases withdrawal-induced hyperalgesia and irritability-like behavior in oxycodone-dependent heterogeneous stock rats.","volume":"13","author":"de Guglielmo","year":"2019","journal-title":"Front. Behav. Neurosci."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000384","article-title":"A large fraction of extragenic RNA pol II transcription sites overlap enhancers.","volume":"8","author":"De Santa","year":"2010","journal-title":"PLoS Biol."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-020-03739-4","article-title":"MEIRLOP: improving score-based motif enrichment by incorporating sequence bias covariates.","volume":"21","author":"Delos Santos","year":"2020","journal-title":"BMC Bioinformatics"},{"key":"B26","first-page":"1401","article-title":"Glucocorticoids and behavioral effects of psychostimulants. II: cocaine intravenous self-administration and reinstatement depend on glucocorticoid levels.","volume":"281","author":"Deroche","year":"1997","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B27","doi-asserted-by":"publisher","first-page":"4785","DOI":"10.1523\/JNEUROSCI.23-11-04785.2003","article-title":"The glucocorticoid receptor as a potential target to reduce cocaine abuse.","volume":"23","author":"Deroche-Gamonet","year":"2003","journal-title":"J. Neurosci."},{"key":"B28","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/s41586-021-03670-5","article-title":"Molecular logic of cellular diversification in the mouse cerebral cortex","volume":"595","author":"Di Bella","year":"2021","journal-title":"Nature"},{"key":"B29","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0166-4328(02)00286-3","article-title":"Nucleus accumbens shell and core dopamine: differential role in behavior and addiction","volume":"137","author":"Di Chiara","year":"2002","journal-title":"Behav. Brain Res"},{"key":"B30","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/nature11082","article-title":"Topological domains in mammalian genomes identified by analysis of chromatin interactions.","volume":"485","author":"Dixon","year":"2012","journal-title":"Nature"},{"key":"B31","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner.","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"B32","doi-asserted-by":"publisher","first-page":"10867","DOI":"10.1523\/JNEUROSCI.1821-17.2017","article-title":"Circuit and synaptic plasticity mechanisms of drug relapse.","volume":"37","author":"Dong","year":"2017","journal-title":"J. Neurosci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1836","DOI":"10.1101\/gr.253492.119","article-title":"Identification and dynamic quantification of regulatory elements using total RNA.","volume":"29","author":"Duttke","year":"2019","journal-title":"Genome Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/nature09906","article-title":"Mapping and analysis of chromatin state dynamics in nine human cell types.","volume":"473","author":"Ernst","year":"2011","journal-title":"Nature"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1111\/ejn.12644","article-title":"Neural and psychological mechanisms underlying compulsive drug seeking habits and drug memories\u2013indications for novel treatments of addiction.","volume":"40","author":"Everitt","year":"2014","journal-title":"Eur. J. Neurosci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2406","DOI":"10.1111\/acer.14192","article-title":"Prevalence and correlates of past-year recovery from dsm-5 alcohol use disorder: results from national epidemiologic survey on alcohol and related conditions-III.","volume":"43","author":"Fan","year":"2019","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1111\/adb.12381","article-title":"Sex differences in impulsive and compulsive behaviors: a focus on drug addiction.","volume":"21","author":"Fattore","year":"2016","journal-title":"Addict. Biol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"3100","DOI":"10.1523\/JNEUROSCI.4012-14.2015","article-title":"SIRT1-FOXO3a regulate cocaine actions in the nucleus accumbens.","volume":"35","author":"Ferguson","year":"2015","journal-title":"J. Neurosci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.neubiorev.2010.05.002","article-title":"Individual differences in prefrontal cortex function and the transition from drug use to drug dependence.","volume":"35","author":"George","year":"2010","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2474","DOI":"10.1038\/sj.npp.1301626","article-title":"Extended access to cocaine self-administration produces long-lasting prefrontal cortex-dependent working memory impairments.","volume":"33","author":"George","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.neuropharm.2013.04.032","article-title":"Rapid, transient synaptic plasticity in addiction.","author":"Gipson","year":"2014","journal-title":"Neuropharmacology"},{"key":"B42","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/nrn3119","article-title":"Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications","volume":"12","author":"Goldstein","year":"2011","journal-title":"Nat. Rev. Neurosci"},{"key":"B43","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.conb.2019.05.005","article-title":"Epigenetics and addiction.","volume":"59","author":"Hamilton","year":"2019","journal-title":"Curr. Opin. Neurobiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","article-title":"Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities.","volume":"38","author":"Heinz","year":"2010","journal-title":"Mol. Cell"},{"key":"B45","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1038\/nrm3949","article-title":"The selection and function of cell type-specific enhancers.","volume":"16","author":"Heinz","year":"2015","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1016\/j.cell.2018.07.047","article-title":"Transcription elongation can affect genome 3D structure.","volume":"174","author":"Heinz","year":"2018","journal-title":"Cell"},{"key":"B47","doi-asserted-by":"publisher","first-page":"12316","DOI":"10.1073\/pnas.1603217113","article-title":"Nascent RNA sequencing reveals distinct features in plant transcription.","volume":"113","author":"Hetzel","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B48","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/0896-6273(94)90061-2","article-title":"Induction of a long-lasting AP-1 complex composed of altered Fos-like proteins in brain by chronic cocaine and other chronic treatments.","volume":"13","author":"Hope","year":"1994","journal-title":"Neuron"},{"key":"B49","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/nn.4170","article-title":"Stimulus-specific combinatorial functionality of neuronal c-fos enhancers.","volume":"19","author":"Joo","year":"2016","journal-title":"Nat. Neurosci."},{"key":"B50","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.molcel.2013.07.010","article-title":"Remodeling of the enhancer landscape during macrophage activation is coupled to enhancer transcription.","volume":"51","author":"Kaikkonen","year":"2013","journal-title":"Mol. Cell"},{"key":"B51","doi-asserted-by":"publisher","first-page":"2140","DOI":"10.1073\/pnas.1915143117","article-title":"Nociceptin attenuates the escalation of oxycodone self-administration by normalizing CeA-GABA transmission in highly addicted rats.","volume":"117","author":"Kallupi","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B52","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1038\/nature09033","article-title":"Widespread transcription at neuronal activity-regulated enhancers.","volume":"465","author":"Kim","year":"2010","journal-title":"Nature"},{"key":"B53","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1016\/S2215-0366(16)00104-8","article-title":"Neurobiology of addiction: a neurocircuitry analysis.","volume":"3","author":"Koob","year":"2016","journal-title":"Lancet Psychiatry"},{"key":"B54","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.neuropharm.2013.05.024","article-title":"Addiction as a stress surfeit disorder.","author":"Koob","year":"2014","journal-title":"Neuropharmacology"},{"key":"B55","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/npp.2016.121","article-title":"Glial and neuroimmune mechanisms as critical modulators of drug use and abuse.","volume":"42","author":"Lacagnina","year":"2017","journal-title":"Neuropsychopharmacology"},{"key":"B56","doi-asserted-by":"publisher","first-page":"R754","DOI":"10.1016\/j.cub.2010.06.070","article-title":"Transcriptional enhancers in animal development and evolution.","volume":"20","author":"Levine","year":"2010","journal-title":"Curr. Biol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/nrg.2016.4","article-title":"Enhancers as non-coding RNA transcription units: recent insights and future perspectives.","volume":"17","author":"Li","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"B58","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s41586-021-03604-1","article-title":"An atlas of gene regulatory elements in adult mouse cerebrum","volume":"598","author":"Li","year":"2021","journal-title":"Nature"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-2-r11","article-title":"Candidate genes for alcohol preference identified by expression profiling in alcohol-preferring and -nonpreferring reciprocal congenic rats.","volume":"11","author":"Liang","year":"2010","journal-title":"Genome Biol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1126\/science.1181369","article-title":"Comprehensive mapping of long-range interactions reveals folding principles of the human genome.","volume":"326","author":"Lieberman-Aiden","year":"2009","journal-title":"Science"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20202733","article-title":"DNMT3A haploinsufficiency causes dichotomous DNA methylation defects at enhancers in mature human immune cells.","volume":"218","author":"Lim","year":"2021","journal-title":"J. Exp. Med."},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2.","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1038\/nn1143","article-title":"Regulation of gene expression and cocaine reward by CREB and \u0394FosB.","volume":"6","author":"McClung","year":"2003","journal-title":"Nat. Neurosci."},{"key":"B64","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nbt.1630","article-title":"GREAT improves functional interpretation of cis-regulatory regions.","volume":"28","author":"McLean","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1101\/gad.308619.117","article-title":"The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription.","volume":"32","author":"Mikhaylichenko","year":"2018","journal-title":"Genes Dev."},{"key":"B66","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/nrg2957","article-title":"Enhancer function: new insights into the regulation of tissue-specific gene expression.","volume":"12","author":"Ong","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"B67","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.cell.2012.12.018","article-title":"Latent enhancers activated by stimulation in differentiated cells.","volume":"152","author":"Ostuni","year":"2013","journal-title":"Cell"},{"key":"B68","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1093\/cercor\/10.3.326","article-title":"Orbital and medial prefrontal cortex and psychostimulant abuse: studies in animal models","volume":"10","author":"Porrino","year":"2000","journal-title":"Cereb. Cortex"},{"key":"B69","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1038\/s41386-018-0008-x","article-title":"Environmental, genetic and epigenetic contributions to cocaine addiction.","volume":"43","author":"Pierce","year":"2018","journal-title":"Neuropsychopharmacology"},{"key":"B70","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.tins.2010.02.002","article-title":"The addicted synapse: mechanisms of synaptic and structural plasticity in nucleus accumbens.","volume":"33","author":"Russo","year":"2010","journal-title":"Trends Neurosci."},{"key":"B71","doi-asserted-by":"publisher","first-page":"9991","DOI":"10.1073\/pnas.1920866117","article-title":"Cannabinoid exposure in rat adolescence reprograms the initial behavioral, molecular, and epigenetic response to cocaine.","volume":"117","author":"Scherma","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B72","doi-asserted-by":"publisher","first-page":"3423","DOI":"10.1007\/s00213-021-05961-1","article-title":"Individual differences in addiction-like behaviors and choice between cocaine versus food in Heterogeneous Stock rats.","volume":"238","author":"Sedighim","year":"2021","journal-title":"Psychopharmacology"},{"key":"B73","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1101\/gr.152140.112","article-title":"Patterns of regulatory activity across diverse human cell types predict tissue identity, transcription factor binding, and long-range interactions.","volume":"23","author":"Sheffield","year":"2013","journal-title":"Genome Res."},{"key":"B74","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1038\/s41386-019-0450-4","article-title":"Astrocytes determine conditioned response to morphine via glucocorticoid receptor-dependent regulation of lactate release.","volume":"45","author":"Skupio","year":"2020","journal-title":"Neuropsychopharmacology"},{"key":"B75","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1002\/glia.22460","article-title":"Astrocytes are a neural target of morphine action via glucocorticoid receptor-dependent signaling.","volume":"61","author":"Slezak","year":"2013","journal-title":"Glia"},{"key":"B76","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1007\/978-1-4939-9581-3_11","article-title":"Using heterogeneous stocks for fine-mapping genetically complex traits.","volume":"2018","author":"Solberg Woods","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2013.00068","article-title":"The role of the glucocorticoids in developing resilience to stress and addiction.","volume":"4","author":"Srinivasan","year":"2013","journal-title":"Front. Psychiatry"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a040253","article-title":"Epigenetics of drug addiction.","volume":"11","author":"Stewart","year":"2021","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"B79","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1038\/s41592-021-01282-5","article-title":"Single-cell chromatin state analysis with Signac.","volume":"18","author":"Stuart","year":"2021","journal-title":"Nat. Methods"},{"key":"B80","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1038\/s41380-021-01163-5","article-title":"Key transcription factors mediating cocaine-induced plasticity in the nucleus accumbens.","volume":"27","author":"Teague","year":"2021","journal-title":"Mol. Psychiatry."},{"key":"B81","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1016\/j.neuron.2015.03.033","article-title":"LRP8-reelin-regulated neuronal enhancer signature underlying learning and memory formation.","volume":"86","author":"Telese","year":"2015","journal-title":"Neuron"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-021-02469-x","article-title":"AMULET: a novel read count-based method for effective multiplet detection from single nucleus ATAC-seq data.","volume":"22","author":"Thibodeau","year":"2021","journal-title":"Genome Biol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"7563","DOI":"10.1523\/JNEUROSCI.0069-12.2012","article-title":"Corticosteroid-dependent plasticity mediates compulsive alcohol drinking in rats.","volume":"32","author":"Vendruscolo","year":"2012","journal-title":"J. Neurosci."},{"key":"B84","doi-asserted-by":"publisher","first-page":"3193","DOI":"10.1172\/JCI79828","article-title":"Glucocorticoid receptor antagonism decreases alcohol seeking in alcohol-dependent individuals.","volume":"125","author":"Vendruscolo","year":"2015","journal-title":"J. Clin. Invest."},{"key":"B85","doi-asserted-by":"crossref","first-page":"3932","DOI":"10.1523\/JNEUROSCI.0433-05.2005","article-title":"Activation of orbital and medial prefrontal cortex by methylphenidate in cocaine-addicted subjects but not in controls: relevance to addiction","volume":"25","author":"Volkow","year":"2015","journal-title":"J. Neurosci"},{"key":"B86","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41588-022-01026-x","article-title":"Prediction of histone post-translational modification patterns based on nascent transcription data","volume":"54","author":"Wang","year":"2022","journal-title":"Nat. Genet"},{"key":"B87","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.biopsych.2020.08.005","article-title":"Epigenetic mechanisms in drug relapse.","volume":"89","author":"Werner","year":"2021","journal-title":"Biol. Psychiatry"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.603445","article-title":"Toll-like receptor 4 signaling and drug addiction.","volume":"11","author":"Wu","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B89","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/s41586-021-03500-8","article-title":"A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex","volume":"598","author":"Yao","year":"2021","journal-title":"Nature"},{"key":"B90","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1038\/nn1636","article-title":"An essential role for \u0394FosB in the nucleus accumbens in morphine action.","volume":"9","author":"Zachariou","year":"2006","journal-title":"Nat. Neurosci."},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137","article-title":"Model-based analysis of ChIP-Seq (MACS).","volume":"9","author":"Zhang","year":"2008","journal-title":"Genome Biology"},{"key":"B92","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s41586-021-03223-w","article-title":"Epigenomic diversity of cortical projection neurons in the mouse brain","volume":"598","author":"Zhang","year":"2021","journal-title":"Nature"},{"key":"B93","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/s41586-021-03209-8","article-title":"Single-cell epigenomics reveals mechanisms of human cortical development","volume":"598","author":"Ziffra","year":"2021","journal-title":"Nature"},{"key":"B94","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1111\/j.1521-0391.2014.12147.x","article-title":"Genome-wide association discoveries of alcohol dependence.","volume":"23","author":"Zuo","year":"2014","journal-title":"Am. J. Addict."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2022.858427\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T05:18:49Z","timestamp":1652678329000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2022.858427\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,16]]},"references-count":94,"alternative-id":["10.3389\/fnins.2022.858427"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2022.858427","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.01.12.475507","asserted-by":"object"}]},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,16]]},"article-number":"858427"}}