CoChat
Sign Up
Cited by 993Neurotransmitter Receptor Influence on BehaviorEpigenetics and DNA MethylationNeuroscience and Neuropharmacology Research

Transcriptional and epigenetic mechanisms of addiction

Open access
Robison, Alfred J., Nestler, Eric J.·2011·Nature Reviews Neuroscience
DOI 10.1038/nrn3111PMC PMC3272277
Open this paper in CoChat — free account

Abstract

Investigations of long-term changes in brain structure and function that accompany chronic exposure to drugs of abuse suggest that alterations in gene regulation contribute substantially to the addictive phenotype. Here, we review multiple mechanisms by which drugs alter the transcriptional potential of genes. These mechanisms range from the mobilization or repression of the transcriptional machinery - including the transcription factors ΔFOSB, cyclic AMP-responsive element binding protein (CREB) and nuclear factor-κB (NF-κB) - to epigenetics - including alterations in the accessibility of genes within their native chromatin structure induced by histone tail modifications and DNA methylation, and the regulation of gene expression by non-coding RNAs. Increasing evidence implicates these various mechanisms of gene regulation in the lasting changes that drugs of abuse induce in the brain, and offers novel inroads for addiction therapy.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/nrn3111

Cites

7 of 7 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • TD5 BLNPs may facilitate delivery of mRNAs encoding transcriptional factors to regulate synaptic plasticity and modulate key neurotransmitter systems, thereby mitigating addictive behaviors.

    “Furthermore, TD5 BLNPs may also facilitate delivery of mRNAs encoding transcriptional factors to regulate synaptic plasticity and modulate key neurotransmitter systems, thereby mitigating addictive behaviors.[32]”

    From Lipid Nanoparticles Enhance mRNA Delivery to the Central Nervous System Upon Intrathecal Injection (2025) · cites this paper as [32]

    The ΔFosB subsection (page unavailable) links a transcription factor to cocaine-induced structural plasticity and glutamatergic synaptic function. The paper also discusses gene regulation and addiction-related behavior, but our copy does not address TD5 BLNPs, delivery of transcription-factor mRNAs, or whether such delivery mitigates addictive behavior. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 136

  1. [1]Kendler KS Myers J Prescott CA Specificity of genetic and environmental risk factors for symptoms of cannabis, cocaine, alcohol, caffeine, and nicotine dependence Arch Gen Psychiatry 64 1313 1320 64/11/1313 [pii] 10.1001/archpsyc.64.11.1313 2007 17984400 · DOI
  2. [2]Volkow N Rutter J Pollock JD Shurtleff D Baler R One SNP linked to two diseases-addiction and cancer: a double whammy? Nicotine addiction and lung cancer susceptibility Mol Psychiatry 13 990 992 mp200871 [pii] 10.1038/mp.2008.71 2008 18936755 PMC4827504 · DOI
  3. [3]Goldman D Oroszi G Ducci F The genetics of addictions: uncovering the genes Nat Rev Genet 6 521 532 nrg1635 [pii] 10.1038/nrg1635 2005 15995696 · DOI · Paper page
  4. [4]Henikoff S Matzke MA Exploring and explaining epigenetic effects Trends Genet 13 293 295 S0168952597012195 [pii] 1997 9260513
  5. [5]Sutherland JE Costa M Epigenetics and the environment Ann N Y Acad Sci 983 151 160 2003 12724220
  6. [6]Fraga MF Epigenetic differences arise during the lifetime of monozygotic twins Proc Natl Acad Sci U S A 102 10604 10609 0500398102 [pii] 10.1073/pnas.0500398102 2005 16009939 PMC1174919 · DOI · Paper page
  7. [7]Koob GF Le Moal M Neurobiology of Addiction Academic Press 2005
  8. [8]Kalivas PW Volkow ND The neural basis of addiction: a pathology of motivation and choice Am J Psychiatry 162 1403 1413 162/8/1403 [pii] 10.1176/appi.ajp.162.8.1403 2005 16055761 · DOI · Paper page
  9. [9]Hyman SE Malenka RC Nestler EJ Neural mechanisms of addiction: the role of reward-related learning and memory Annu Rev Neurosci 29 565 598 10.1146/annurev.neuro.29.051605.113009 2006 16776597 · DOI · Paper page
  10. [10]Robinson TE Berridge KC The neural basis of drug craving: an incentive-sensitization theory of addiction Brain Res Brain Res Rev 18 247 291 1993 8401595
  11. [11]Nestler EJ Molecular basis of long-term plasticity underlying addiction Nat Rev Neurosci 2 119 128 10.1038/35053570 2001 11252991 · DOI
  12. [12]Andersen SL Teicher MH Desperately driven and no brakes: developmental stress exposure and subsequent risk for substance abuse Neurosci Biobehav Rev 33 516 524 S0149-7634(08)00166-8 [pii] 10.1016/j.neubiorev.2008.09.009 2009 18938197 PMC2688959 · DOI · Paper page
  13. [13]Malanga CJ Kosofsky BE Does drug abuse beget drug abuse? Behavioral analysis of addiction liability in animal models of prenatal drug exposure Brain Res Dev Brain Res 147 47 57 S0165380603003079 [pii] 2003 14741750
  14. [14]Nestler EJ Review Transcriptional mechanisms of addiction: role of DeltaFosB Philos Trans R Soc Lond B Biol Sci 363 3245 3255 925643J51371U6N7 [pii] 10.1098/rstb.2008.0067 2008 18640924 PMC2607320 · DOI
  15. [15]Jorissen HJ Dimerization and DNA-binding properties of the transcription factor DeltaFosB Biochemistry 46 8360 8372 10.1021/bi700494v 2007 17580968 · DOI
  16. [16]Perrotti LI Distinct patterns of DeltaFosB induction in brain by drugs of abuse Synapse 62 358 369 10.1002/syn.20500 2008 18293355 PMC2667282 · DOI
  17. [17]Hiroi N FosB mutant mice: loss of chronic cocaine induction of Fos-related proteins and heightened sensitivity to cocaine’s psychomotor and rewarding effects Proc Natl Acad Sci U S A 94 10397 10402 1997 9294222 PMC23374
  18. [18]Carle TL Proteasome-dependent and -independent mechanisms for FosB destabilization: identification of FosB degron domains and implications for DeltaFosB stability Eur J Neurosci 25 3009 3019 EJN5575 [pii] 10.1111/j.1460-9568.2007.05575.x 2007 17561814 · DOI
  19. [19]Ulery PG Rudenko G Nestler EJ Regulation of DeltaFosB stability by phosphorylation J Neurosci 26 5131 5142 26/19/5131 [pii] 10.1523/JNEUROSCI.4970-05.2006 2006 16687504 PMC6674239 · DOI
  20. [20]Ulery-Reynolds PG Castillo MA Vialou V Russo SJ Nestler EJ Phosphorylation of DeltaFosB mediates its stability in vivo Neuroscience 158 369 372 S0306-4522(08)01596-0 [pii] 10.1016/j.neuroscience.2008.10.059 2009 19041372 PMC2734485 · DOI
  21. [21]Kelz MB Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine Nature 401 272 276 10.1038/45790 1999 10499584 · DOI · Paper page
  22. [22]Zachariou V An essential role for DeltaFosB in the nucleus accumbens in morphine action Nat Neurosci 9 205 211 nn1636 [pii] 10.1038/nn1636 2006 16415864 · DOI
  23. [23]Colby CR Whisler K Steffen C Nestler EJ Self DW Striatal cell type-specific overexpression of DeltaFosB enhances incentive for cocaine J Neurosci 23 2488 2493 23/6/2488 [pii] 2003 12657709 PMC6742034
  24. [24]Winstanley CA DeltaFosB induction in orbitofrontal cortex mediates tolerance to cocaine-induced cognitive dysfunction J Neurosci 27 10497 10507 27/39/10497 [pii] 10.1523/JNEUROSCI.2566-07.2007 2007 17898221 PMC6673166 · DOI
  25. [25]Winstanley CA DeltaFosB induction in orbitofrontal cortex potentiates locomotor sensitization despite attenuating the cognitive dysfunction caused by cocaine Pharmacol Biochem Behav 93 278 284 S0091-3057(08)00402-4 [pii] 10.1016/j.pbb.2008.12.007 2009 19135469 PMC2820241 · DOI
  26. [26]Werme M Delta FosB regulates wheel running J Neurosci 22 8133 8138 22/18/8133 [pii] 2002 12223567 PMC6758121
  27. [27]Wallace DL The influence of DeltaFosB in the nucleus accumbens on natural reward-related behavior J Neurosci 28 10272 10277 28/41/10272 [pii] 10.1523/JNEUROSCI.1531-08.2008 2008 18842886 PMC2653197 · DOI
  28. [28]Teegarden SL Nestler EJ Bale TL Delta FosB-mediated alterations in dopamine signaling are normalized by a palatable high-fat diet Biol Psychiatry 64 941 950 S0006-3223(08)00704-X [pii] 10.1016/j.biopsych.2008.06.007 2008 18657800 PMC2582592 · DOI
  29. [29]Hedges VL Chakravarty S Nestler EJ Meisel RL Delta FosB overexpression in the nucleus accumbens enhances sexual reward in female Syrian hamsters Genes Brain Behav 8 442 449 GBB491 [pii] 10.1111/j.1601-183X.2009.00491.x 2009 19566711 PMC2736637 · DOI
  30. [30]Pitchers KK DeltaFosB in the nucleus accumbens is critical for reinforcing effects of sexual reward Genes Brain Behav 9 831 840 10.1111/j.1601-183X.2010.00621.xGBB621 [pii] 2010 20618447 PMC2970635 · DOI
  31. [31]McClung CA Nestler EJ Regulation of gene expression and cocaine reward by CREB and DeltaFosB Nat Neurosci 6 1208 1215 10.1038/nn1143nn1143 [pii] 2003 14566342 · DOI
  32. [32]Renthal W Genome-wide analysis of chromatin regulation by cocaine reveals a role for sirtuins Neuron 62 335 348 S0896-6273(09)00241-4 [pii] 10.1016/j.neuron.2009.03.026 2009 19447090 PMC2779727 · DOI · Paper page
  33. [33]Bibb JA Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5 Nature 410 376 380 10.1038/3506659135066591 [pii] 2001 11268215 · DOI
  34. [35]Robinson TE Kolb B Structural plasticity associated with exposure to drugs of abuse Neuropharmacology 47 Suppl 1 33 46 S0028390804001959 [pii] 10.1016/j.neuropharm.2004.06.025 2004 15464124 · DOI
  35. [36]Kalivas PW The glutamate homeostasis hypothesis of addiction Nat Rev Neurosci 10 561 572 nrn2515 [pii] 10.1038/nrn2515 2009 19571793 · DOI · Paper page
  36. [37]Maze I Essential role of the histone methyltransferase G9a in cocaine-induced plasticity Science 327 213 216 327/5962/213 [pii] 10.1126/science.1179438 2010 20056891 PMC2820240 · DOI · Paper page
  37. [38]Vialou V DeltaFosB in brain reward circuits mediates resilience to stress and antidepressant responses Nat Neurosci 13 745 752 nn.2551 [pii] 10.1038/nn.2551 2010 20473292 PMC2895556 · DOI · Paper page
  38. [40]Wolf ME Ferrario CR AMPA receptor plasticity in the nucleus accumbens after repeated exposure to cocaine Neurosci Biobehav Rev 35 185 211 S0149-7634(10)00014-X [pii] 10.1016/j.neubiorev.2010.01.013 2010 20109488 PMC2962767 · DOI · Paper page
  39. [41]Carlezon WA Jr Duman RS Nestler EJ The many faces of CREB Trends Neurosci 28 436 445 S0166-2236(05)00158-X [pii] 10.1016/j.tins.2005.06.005 2005 15982754 · DOI
  40. [42]Briand LA Blendy JA Molecular and genetic substrates linking stress and addiction Brain Res 1314 219 234 S0006-8993(09)02394-4 [pii] 10.1016/j.brainres.2009.11.002 2010 19900417 PMC2819611 · DOI · Paper page
  41. [43]Edwards S Graham DL Bachtell RK Self DW Region-specific tolerance to cocaine-regulated cAMP-dependent protein phosphorylation following chronic self-administration Eur J Neurosci 25 2201 2213 EJN5473 [pii] 10.1111/j.1460-9568.2007.05473.x 2007 17439498 · DOI
  42. [44]Carlezon WA Jr Regulation of cocaine reward by CREB Science 282 2272 2275 1998 9856954
  43. [45]Barrot M CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli Proc Natl Acad Sci U S A 99 11435 11440 10.1073/pnas.172091899172091899 [pii] 2002 12165570 PMC123274 · DOI
  44. [46]Larson EB Over-expression of CREB in the nucleus accumbens shell increases cocaine reinforcement in self-administering rats J Neurosci In Press 2011 PMC3229171 22072694
  45. [47]Pluzarev O Pandey SC Modulation of CREB expression and phosphorylation in the rat nucleus accumbens during nicotine exposure and withdrawal J Neurosci Res 77 884 891 10.1002/jnr.20216 2004 15334606 · DOI
  46. [48]Misra K Roy A Pandey SC Effects of voluntary ethanol intake on the expression of Ca(2+)/calmodulin-dependent protein kinase IV and on CREB expression and phosphorylation in the rat nucleus accumbens Neuroreport 12 4133 4137 2001 11742252
  47. [49]Li J Li YH Yuan XR Changes of phosphorylation of cAMP response element binding protein in rat nucleus accumbens after chronic ethanol intake: naloxone reversal Acta Pharmacol Sin 24 930 936 2003 12956944
  48. [50]Brunzell DH Mineur YS Neve RL Picciotto MR Nucleus accumbens CREB activity is necessary for nicotine conditioned place preference Neuropsychopharmacology 34 1993 2001 npp200911 [pii] 10.1038/npp.2009.11 2009 19212318 PMC2709692 · DOI
  49. [51]Rubino T Cellular mechanisms underlying the anxiolytic effect of low doses of peripheral Delta9-tetrahydrocannabinol in rats Neuropsychopharmacology 32 2036 2045 1301330 [pii] 10.1038/sj.npp.1301330 2007 17287821 · DOI
  50. [52]Shiflett MW Mauna JC Chipman AM Peet E Thiels E Appetitive Pavlovian conditioned stimuli increase CREB phosphorylation in the nucleus accumbens Neurobiol Learn Mem 92 451 454 S1074-7427(09)00061-6 [pii] 10.1016/j.nlm.2009.02.010 2009 19248836 PMC2737078 · DOI
  51. [53]Green TA Environmental enrichment produces a behavioral phenotype mediated by low cyclic adenosine monophosphate response element binding (CREB) activity in the nucleus accumbens Biol Psychiatry 67 28 35 S0006-3223(09)00830-0 [pii] 10.1016/j.biopsych.2009.06.022 2010 19709647 PMC2860655 · DOI
  52. [54]Dong Y CREB modulates excitability of nucleus accumbens neurons Nat Neurosci 9 475 477 nn1661 [pii] 10.1038/nn1661 2006 16520736 · DOI
  53. [55]Huang YH CREB modulates the functional output of nucleus accumbens neurons: a critical role of N-methyl-D-aspartate glutamate receptor (NMDAR) receptors J Biol Chem 283 2751 2760 M706578200 [pii] 10.1074/jbc.M706578200 2008 18055458 PMC2535571 · DOI
  54. [56]Meffert MK Chang JM Wiltgen BJ Fanselow MS Baltimore D NF-kappa B functions in synaptic signaling and behavior Nat Neurosci 6 1072 1078 10.1038/nn1110nn1110 [pii] 2003 12947408 · DOI
  55. [57]Russo SJ Nuclear factor kappa B signaling regulates neuronal morphology and cocaine reward J Neurosci 29 3529 3537 29/11/3529 [pii] 10.1523/JNEUROSCI.6173-08.2009 2009 19295158 PMC2677656 · DOI
  56. [58]Sullivan PF Candidate genes for nicotine dependence via linkage, epistasis, and bioinformatics Am J Med Genet B Neuropsychiatr Genet 126B 23 36 10.1002/ajmg.b.20138 2004 15048644 · DOI
  57. [61]Chen L Chronic ethanol feeding impairs AMPK and MEF2 expression and is associated with GLUT4 decrease in rat myocardium Exp Mol Med 42 205 215 emm.2010.42.021 [pii] 2010 20164678 PMC2845005
  58. [62]Ambroggi F Stress and addiction: glucocorticoid receptor in dopaminoceptive neurons facilitates cocaine seeking Nat Neurosci 12 247 249 nn.2282 [pii] 10.1038/nn.2282 2009 19234455 · DOI
  59. [63]Barik J Glucocorticoid receptors in dopaminoceptive neurons, key for cocaine, are dispensable for molecular and behavioral morphine responses Biol Psychiatry 68 231 239 S0006-3223(10)00400-2 [pii] 10.1016/j.biopsych.2010.03.037 2010 20554270 · DOI
  60. [64]Desrivieres S Glucocorticoid receptor (NR3C1) gene polymorphisms and onset of alcohol abuse in adolescents Addict Biol 16 510 513 10.1111/j.1369-1600.2010.00239.xADB239 [pii] 2011 20731635 PMC3428936 · DOI
  61. [65]McQuown SC Wood MA Epigenetic regulation in substance use disorders Curr Psychiatry Rep 12 145 153 10.1007/s11920-010-0099-5 2010 20425300 PMC2847696 · DOI
  62. [66]Renthal W Nestler EJ Epigenetic mechanisms in drug addiction Trends Mol Med 14 341 350 S1471-4914(08)00135-4 [pii] 10.1016/j.molmed.2008.06.004 2008 18635399 PMC2753378 · DOI
  63. [67]Borrelli E Nestler EJ Allis CD Sassone-Corsi P Decoding the epigenetic language of neuronal plasticity Neuron 60 961 974 S0896-6273(08)00885-4 [pii] 10.1016/j.neuron.2008.10.012 2008 19109904 PMC2737473 · DOI
  64. [68]Berger SL The complex language of chromatin regulation during transcription Nature 447 407 412 nature05915 [pii] 10.1038/nature05915 2007 17522673 · DOI · Paper page
  65. [69]Jenuwein T Allis CD Translating the histone code Science 293 1074 1080 10.1126/science.1063127293/5532/1074 [pii] 2001 11498575 · DOI
  66. [70]Maze I Nestler EJ The epigenetic landscape of addiction Ann N Y Acad Sci 1216 99 113 10.1111/j.1749-6632.2010.05893.x 2011 21272014 PMC3071632 · DOI
  67. [71]Su IH Tarakhovsky A Lysine methylation and ‘signaling memory’ Curr Opin Immunol 18 152 157 S0952-7915(06)00010-0 [pii] 10.1016/j.coi.2006.01.012 2006 16464568 · DOI
  68. [72]Rumbaugh G Miller CA Epigenetic changes in the brain: measuring global histone modifications Methods Mol Biol 670 263 274 10.1007/978-1-60761-744-0_18 2011 20967596 PMC3235043 · DOI
  69. [73]Kumar A Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum Neuron 48 303 314 S0896-6273(05)00790-7 [pii] 10.1016/j.neuron.2005.09.023 2005 16242410 · DOI · Paper page
  70. [75]Bertran-Gonzalez J Opposing patterns of signaling activation in dopamine D1 and D2 receptor-expressing striatal neurons in response to cocaine and haloperidol J Neurosci 28 5671 5685 28/22/5671 [pii] 10.1523/JNEUROSCI.1039-08.2008 2008 18509028 PMC6670792 · DOI
  71. [76]Pandey SC Ugale R Zhang H Tang L Prakash A Brain chromatin remodeling: a novel mechanism of alcoholism J Neurosci 28 3729 3737 28/14/3729 [pii] 10.1523/JNEUROSCI.5731-07.2008 2008 18385331 PMC6671100 · DOI
  72. [77]Wang Y Krishnan HR Ghezzi A Yin JC Atkinson NS Drug-induced epigenetic changes produce drug tolerance PLoS Biol 5 e265 07-PLBI-RA-0430 [pii] 10.1371/journal.pbio.0050265 2007 17941717 PMC2020501 · DOI
  73. [78]Khare M Taylor AH Konje JC Bell SC Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription Mol Hum Reprod 12 321 333 gal036 [pii] 10.1093/molehr/gal036 2006 16597638 · DOI
  74. [79]Parmentier-Batteur S Jin K Xie L Mao XO Greenberg DA DNA microarray analysis of cannabinoid signaling in mouse brain in vivo Mol Pharmacol 62 828 835 2002 12237329
  75. [80]Renthal W Histone deacetylase 5 epigenetically controls behavioral adaptations to chronic emotional stimuli Neuron 56 517 529 S0896-6273(07)00766-0 [pii] 10.1016/j.neuron.2007.09.032 2007 17988634 · DOI · Paper page
  76. [81]Romieu P Histone deacetylase inhibitors decrease cocaine but not sucrose self-administration in rats J Neurosci 28 9342 9348 28/38/9342 [pii] 10.1523/JNEUROSCI.0379-08.2008 2008 18799668 PMC6671106 · DOI
  77. [82]Kim WY Kim S Kim JH Chronic microinjection of valproic acid into the nucleus accumbens attenuates amphetamine-induced locomotor activity Neurosci Lett 432 54 57 S0304-3940(07)01261-X [pii] 10.1016/j.neulet.2007.12.005 2008 18164815 · DOI
  78. [83]Levine AA CREB-binding protein controls response to cocaine by acetylating histones at the fosB promoter in the mouse striatum Proc Natl Acad Sci U S A 102 19186 19191 0509735102 [pii] 10.1073/pnas.0509735102 2005 16380431 PMC1323217 · DOI
  79. [84]Finkel T Deng CX Mostoslavsky R Recent progress in the biology and physiology of sirtuins Nature 460 587 591 nature08197 [pii] 10.1038/nature08197 2009 19641587 PMC3727385 · DOI
  80. [85]Wang F Tong Q SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1’s repressive interaction with PPARgamma Mol Biol Cell 20 801 808 E08-06-0647 [pii] 10.1091/mbc.E08-06-0647 2009 19037106 PMC2633403 · DOI
  81. [86]Maze I Cocaine dynamically regulates heterochromatin and repetitive element unsilencing in nucleus accumbens Proc Natl Acad Sci U S A 108 3035 3040 1015483108 [pii] 10.1073/pnas.1015483108 2011 21300862 PMC3041122 · DOI
  82. [91]Renthal W Delta FosB mediates epigenetic desensitization of the c-fos gene after chronic amphetamine exposure J Neurosci 28 7344 7349 28/29/7344 [pii] 10.1523/JNEUROSCI.1043-08.2008 2008 18632938 PMC2610249 · DOI
  83. [92]Newell-Price J Clark AJ King P DNA methylation and silencing of gene expression Trends Endocrinol Metab 11 142 148 S1043-2760(00)00248-4 [pii] 2000 10754536
  84. [93]Kim JK Samaranayake M Pradhan S Epigenetic mechanisms in mammals Cell Mol Life Sci 66 596 612 10.1007/s00018-008-8432-4 2009 18985277 PMC2780668 · DOI
  85. [94]Bird A The methyl-CpG-binding protein MeCP2 and neurological disease Biochem Soc Trans 36 575 583 BST0360575 [pii] 10.1042/BST0360575 2008 18631120 · DOI
  86. [95]Wang Y Leung FC An evaluation of new criteria for CpG islands in the human genome as gene markers Bioinformatics 20 1170 1177 10.1093/bioinformatics/bth059bth059 [pii] 2004 14764558 · DOI
  87. [96]Guo JU Su Y Zhong C Ming GL Song H Hydroxylationof 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain Cell 145 423 434 S0092-8674(11)00299-6 [pii] 10.1016/j.cell.2011.03.022 2011 21496894 PMC3088758 · DOI
  88. [98]Wu H Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells Nature 473 389 393 nature09934 [pii] 10.1038/nature09934 2011 21451524 PMC3539771 · DOI · Paper page
  89. [100]Ficz G Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation Nature 473 398 402 nature10008 [pii] 10.1038/nature10008 2011 21460836 · DOI
  90. [101]Host L Dietrich JB Carouge D Aunis D Zwiller J Cocaine self-administration alters the expression of chromatin-remodelling proteins; modulation byhistone deacetylase inhibition J Psychopharmacol 25 222 229 0269881109348173 [pii] 10.1177/0269881109348173 2011 19939859 · DOI
  91. [102]Cassel S Fluoxetine and cocaine induce the epigenetic factors MeCP2 and MBD1 in adult rat brain Mol Pharmacol 70 487 492 mol.106.022301 [pii] 10.1124/mol.106.022301 2006 16670375 · DOI
  92. [103]Deng JV MeCP2 in the nucleus accumbens contributes to neural and behavioral responses to psychostimulants Nat Neurosci 13 1128 1136 nn.2614 [pii] 10.1038/nn.2614 2010 20711186 PMC2928851 · DOI · Paper page
  93. [104]Grigoryev YA Deconvoluting post-transplant immunity: cell subset-specific mapping reveals pathways for activation and expansion of memory T, monocytes and B cells PLoS One 5 e13358 10.1371/journal.pone.0013358 2010 20976225 PMC2954794 · DOI
  94. [105]Im HI Hollander JA Bali P Kenny PJ MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212 Nat Neurosci 13 1120 1127 nn.2615 [pii] 10.1038/nn.2615 2010 20711185 PMC2928848 · DOI
  95. [106]Graham DL Dynamic BDNF activity in nucleus accumbens with cocaine use increases self-administration and relapse Nat Neurosci 10 1029 1037 nn1929 [pii] 10.1038/nn1929 2007 17618281 · DOI
  96. [107]LaPlant Q Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens Nat Neurosci 13 1137 1143 nn.2619 [pii] 10.1038/nn.2619 2010 20729844 PMC2928863 · DOI · Paper page
  97. [109]Taft RJ Pang KC Mercer TR Dinger M Mattick JS Non-coding RNAs: regulators of disease J Pathol 220 126 139 10.1002/path.2638 2010 19882673 · DOI
  98. [110]Li MD van der Vaart AD MicroRNAs in addiction: adaptation’s middlemen? Mol Psychiatry mp201158 [pii] 10.1038/mp.2011.58 2011 PMC4251867 21606928 · DOI
  99. [111]Hollander JA Striatal microRNA controls cocaine intake through CREB signalling Nature 466 197 202 nature09202 [pii] 10.1038/nature09202 2010 20613834 PMC2916751 · DOI
  100. [112]Chandrasekar V Dreyer JL microRNAs miR-124, let-7d and miR-181a regulate cocaine-induced plasticity Mol Cell Neurosci 42 350 362 S1044-7431(09)00190-0 [pii] 10.1016/j.mcn.2009.08.009 2009 19703567 · DOI
  101. [113]Chandrasekar V Dreyer JL Regulation of MiR-124, Let-7d, and MiR-181a in the accumbens affects the expression, extinction, and reinstatement of cocaine-induced conditioned place preference Neuropsychopharmacology 36 1149 1164 npp2010250 [pii] 10.1038/npp.2010.250 2011 21307844 PMC3079833 · DOI
  102. [114]Sanchez-Simon FM Zhang XX Loh HH Law PY Rodriguez RE Morphine regulates dopaminergic neuron differentiation via miR-133b Mol Pharmacol 78 935 942 mol.110.066837 [pii] 10.1124/mol.110.066837 2010 20716624 PMC2981367 · DOI
  103. [115]Schaefer A Argonaute 2 in dopamine 2 receptor-expressing neurons regulates cocaine addiction J Exp Med 207 1843 1851 jem.20100451 [pii] 10.1084/jem.20100451 2010 20643829 PMC2931161 · DOI
  104. [116]Zheng H mu-Opioid receptor agonists differentially regulate the expression of miR-190 and NeuroD Mol Pharmacol 77 102 109 mol.109.060848 [pii] 10.1124/mol.109.060848 2010 19854889 PMC2802427 · DOI
  105. [117]He Y Yang C Kirkmire CM Wang ZJ Regulation of opioid tolerance by let-7 family microRNA targeting the mu opioid receptor J Neurosci 30 10251 10258 30/30/10251 [pii] 10.1523/JNEUROSCI.2419-10.2010 2010 20668208 PMC2943348 · DOI
  106. [118]Pietrzykowski AZ Posttranscriptional regulation of BK channel splice variant stability by miR-9 underlies neuroadaptation to alcohol Neuron 59 274 287 S0896-6273(08)00529-1 [pii] 10.1016/j.neuron.2008.05.032 2008 18667155 PMC2714263 · DOI
  107. [119]Pietrzykowski AZ The role of microRNAs in drug addiction: a big lesson from tiny molecules Int Rev Neurobiol 91 1 24 S0074-7742(10)91001-5 [pii] 10.1016/S0074-7742(10)91001-5 2010 20813238 · DOI
  108. [120]Eipper-Mains JE microRNA-Seq reveals cocaine-regulated expression of striatal microRNAs RNA rna.2775511 [pii] 10.1261/rna.2775511 2011 PMC3153976 21708909 · DOI
  109. [121]Pelloux Y Everitt BJ Dickinson A Compulsive drug seeking by rats under punishment: effects of drug taking history Psychopharmacology (Berl) 194 127 137 10.1007/s00213-007-0805-0 2007 17514480 · DOI
  110. [122]Pickens CL Neurobiology of the incubation of drug craving Trends Neurosci 34 411 420 S0166-2236(11)00089-0 [pii] 10.1016/j.tins.2011.06.001 2011 21764143 PMC3152666 · DOI
  111. [123]O’Connor EC Chapman K Butler P Mead AN The predictive validity of the rat self-administration model for abuse liability Neurosci Biobehav Rev 35 912 938 S0149-7634(10)00176-4 [pii] 10.1016/j.neubiorev.2010.10.012 2011 21036191 · DOI
  112. [124]Laganiere J An engineered zinc finger protein activator of the endogenous glial cell line-derived neurotrophic factor gene provides functional neuroprotection in a rat model of Parkinson’s disease J Neurosci 30 16469 16474 30/49/16469 [pii] 10.1523/JNEUROSCI.2440-10.2010 2010 21147986 PMC6634881 · DOI
  113. [125]Zhang F Efficient construction of sequence-specific TAL effectors for modulating mammalian transcription Nat Biotechnol 29 149 153 nbt.1775 [pii] 10.1038/nbt.1775 2011 21248753 PMC3084533 · DOI
  114. [126]Cheung I Developmental regulation and individual differences of neuronal H3K4me3 epigenomes in the prefrontal cortex Proc Natl Acad Sci U S A 107 8824 8829 1001702107 [pii] 10.1073/pnas.1001702107 2010 20421462 PMC2889328 · DOI · Paper page
  115. [127]Philibert RA The effect of smoking on MAOA promoter methylation in DNA prepared from lymphoblasts and whole blood Am J Med Genet B Neuropsychiatr Genet 153B 619 628 10.1002/ajmg.b.31031 2010 19777560 PMC3694401 · DOI
  116. [128]Launay JM Smoking induces long-lasting effects through a monoamine-oxidase epigenetic regulation PLoS One 4 e7959 10.1371/journal.pone.0007959 2009 19956754 PMC2775922 · DOI
  117. [129]Philibert RA Gunter TD Beach SR Brody GH Madan A MAOA methylation is associated with nicotine and alcohol dependence in women Am J Med Genet B Neuropsychiatr Genet 147B 565 570 10.1002/ajmg.b.30778 2008 18454435 PMC3685146 · DOI
  118. [130]Witten IB Cholinergic interneurons control local circuit activity and cocaine conditioning Science 330 1677 1681 330/6011/1677 [pii] 10.1126/science.1193771 2010 21164015 PMC3142356 · DOI · Paper page
  119. [131]Lobo MK Cell type-specific loss of BDNF signaling mimics optogenetic control of cocaine reward Science 330 385 390 330/6002/385 [pii] 10.1126/science.1188472 2010 20947769 PMC3011229 · DOI · Paper page
  120. [132]Self DW Neve KA The Dopamine Receptors 2010 479 524 Humana Press 2010
  121. [133]Lee KW Cocaine-induced dendritic spine formation in D1 and D2 dopamine receptor-containing medium spiny neurons in nucleus accumbens Proc Natl Acad Sci U S A 103 3399 3404 0511244103 [pii] 10.1073/pnas.0511244103 2006 16492766 PMC1413917 · DOI
  122. [134]Nye HE Hope BT Kelz MB Iadarola M Nestler EJ Pharmacological studiesof the regulation of chronic FOS-related antigen induction by cocaine in the striatum and nucleus accumbens J Pharmacol Exp Ther 275 1671 1680 1995 8531143
  123. [136]Singla S Kreitzer AC Malenka RC Mechanisms for synapse specificity during striatal long-term depression J Neurosci 27 5260 5264 27/19/5260 [pii] 10.1523/JNEUROSCI.0018-07.2007 2007 17494712 PMC6672378 · DOI
  124. [137]Li Y Acerbo MJ Robinson TE The induction of behavioural sensitization is associated with cocaine-induced structural plasticity in the core (but not shell) of the nucleus accumbens Eur J Neurosci 20 1647 1654 10.1111/j.1460-9568.2004.03612.xEJN3612 [pii] 2004 15355332 · DOI
  125. [138]Russo SJ Mazei-Robison MS Ables JL Nestler EJ Neurotrophic factors and structural plasticity in addiction Neuropharmacology 56 Suppl 1 73 82 S0028-3908(08)00214-1 [pii] 10.1016/j.neuropharm.2008.06.059 2009 18647613 PMC2635335 · DOI
  126. [139]Van Bockstaele EJ Reyes BA Valentino RJ The locus coeruleus: A key nucleus where stress and opioids intersect to mediate vulnerability to opiate abuse Brain Res 1314 162 174 S0006-8993(09)01939-8 [pii] 10.1016/j.brainres.2009.09.036 2010 19765557 PMC3274960 · DOI
  127. [140]Han MH Role of cAMP response element-binding protein in the rat locus ceruleus: regulation of neuronal activity and opiate withdrawal behaviors J Neurosci 26 4624 4629 26/17/4624 [pii] 10.1523/JNEUROSCI.4701-05.2006 2006 16641242 PMC6674058 · DOI
  128. [141]Cao JL Essential role of the cAMP-cAMP response-element binding protein pathway in opiate-induced homeostatic adaptations of locus coeruleus neurons Proc Natl Acad Sci U S A 107 17011 17016 1010077107 [pii] 10.1073/pnas.1010077107 2010 20837544 PMC2947876 · DOI
  129. [142]Nestler EJ Aghajanian GK Molecular and cellular basis of addiction Science 278 58 63 1997 9311927
  130. [143]Fattore L Altea S Fratta W Sex differences in drug addiction: a review of animal and human studies Womens Health (Lond Engl) 4 51 65 10.2217/17455057.4.1.51 2008 19072451 · DOI
  131. [144]Carroll ME Anker JJ Sex differences and ovarian hormones in animal models of drug dependence Horm Behav 58 44 56 S0018-506X(09)00221-9 [pii] 10.1016/j.yhbeh.2009.10.001 2010 19818789 · DOI
  132. [146]Roth ME Carroll ME Sex differences in the escalation of intravenous cocaine intake following long-or short-access to cocaine self-administration Pharmacol Biochem Behav 78 199 207 10.1016/j.pbb.2004.03.018S0091305704001029 [pii] 2004 15219759 · DOI
  133. [147]Cailhol S Mormede P Strain and sex differences in the locomotor response and behavioral sensitization to cocaine in hyperactive rats Brain Res 842 200 205 S0006-8993(99)01742-4 [pii] 1999 10526110
  134. [148]Robinson TE Becker JB Presty SK Long-term facilitation of amphetamine-induced rotational behaviorand striatal dopamine release produced by a single exposure to amphetamine: sex differences Brain Res 253 231 241 0006-8993(82)90690-4 [pii] 1982 6891283
  135. [149]Hernandez-Avila CA Rounsaville BJ Kranzler HR Opioid-, cannabis-and alcohol-dependent women show more rapid progression to substance abuse treatment Drug Alcohol Depend 74 265 272 10.1016/j.drugalcdep.2004.02.001S0376871604000304 [pii] 2004 15194204 · DOI
  136. [150]Munro CA Sex differences in striatal dopamine release in healthy adults Biol Psychiatry 59 966 974 S0006-3223(06)00133-8 [pii] 10.1016/j.biopsych.2006.01.008 2006 16616726 · DOI

Cited by

Sorted by citations

Authors
Robison, A. J., & Nestler, E. J.
Affiliations
Icahn School of Medicine at Mount Sinai (US)
Corresponding author
Nestler, Eric J.
ORCID
Venue
Nature Reviews Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2011-10-12
Volume
12
Issue
11
Pages
623-637
ISSN
  • 1471-003X (ISSN-L)
  • 1471-0048
DOI
10.1038/nrn3111
PMC
PMC3272277
OpenAlex
W2075527287
Cited by
993
References
7
Citations by year
2026: 30 · 2025: 37 · 2024: 49 · 2023: 44 · 2022: 53 · 2021: 73 · 2020: 59 · 2019: 82 · 2018: 82 · 2017: 91 · 2016: 75 · 2015: 80 · 2014: 84 · 2013: 91 · 2012: 60
FWCI
7.26
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature reviews. Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Mental Health (R01MH051399)
  • National Institute on Drug Abuse (P01DA008227, R01DA014133)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
addiction, chronic drug exposure, gene expression regulation, transcription factors, ΔFosB, CREB, NF-κB, epigenetics, histone modifications, DNA methylation, non-coding RNA, chromatin accessibility
MeSH terms
Animals, Gene Expression Regulation, Humans, Transcription, Genetic, Behavior, Addictive, Substance-Related Disorders, Epigenesis, Genetic

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review