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The Role of Epigenetics in Addiction: Clinical Overview and Recent Updates

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Psychiatric Disorders

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2011))

Abstract

Addiction is an international public health problem. It is a polygenic disorder best understood by accounting for the interplay between genetic and environmental factors. A recent way of perceiving this interaction is through epigenetics, which help grasp the neurobiological changes that occur in addiction and explain its relapsing-remitting nature. It is now known that every cell has a different way of expressing its phenotype, despite a universal DNA sequence. This is particularly true in the central nervous system where environmental factors influence this expression. Three major epigenetic processes have been found to participate in the perpetuation of addiction by changing the state of the chromatin and the degree of gene transcription: histone acetylation and methylation, DNA methylation, and noncoding RNAs. In the animal model literature, substantial evidence exists about the role of these epigenetic changes in the different phases of substance use disorders. This book chapter is a non-systematic literature review of the recent publications tackling the topic of epigenetics in addiction. Even though this evidence remains scarce and relatively poorly systematized, it is a promising foundation for future research of molecules that target specific brain regions and their functions to address core behavioral changes seen in addiction.

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References

  1. WHO (2018) Management of substance abuse: the global burden. WHO, Geneva

    Google Scholar 

  2. Whiteford HA, Ferrari AJ, Degenhardt L, Feigin V, Vos T (2015) The global burden of mental, neurological and substance use disorders: an analysis from the global burden of disease study 2010. PLos One 10:e0116820

    PubMed  PubMed Central  Google Scholar 

  3. NIDA (2018) Principles of drug addiction treatment: a research-based guide, 3rd edn. NIDA, Bethesda, MD

    Google Scholar 

  4. Goldman D (1993) Recent developments in alcoholism:genetic transmission. Recent Dev Alcohol 11:231–248

    CAS  PubMed  Google Scholar 

  5. Enoch MA, Goldman D (1999) Genetics of alcoholism and substance abuse. Psychiatr Clin North Am 22:289–299. viii

    CAS  PubMed  Google Scholar 

  6. Dick DM, Foroud T (2003) Candidate genes for alcohol dependence: a review of genetic evidence from human studies. Alcohol Clin Exp Res 27:868–879

    PubMed  Google Scholar 

  7. Koob GF, Le Moal M (2005) Plasticity of reward neurocircuitry and the ‘dark side’ of drug addiction. Nat Neurosci 8:1442–1444

    CAS  PubMed  Google Scholar 

  8. Nestler EJ (2001) Molecular basis of long-term plasticity underlying addiction. Nat Rev Neurosci 2:119–128

    CAS  PubMed  Google Scholar 

  9. Koob GF, Volkow ND (2010) Neurocircuitry of addiction. Neuropsychopharmacology 35:217–238

    PubMed  Google Scholar 

  10. Maze I, Nestler EJ (2011) The epigenetic landscape of addiction. Ann N Y Acad Sci 1216:99–113

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Russo SJ, Dietz DM, Dumitriu D, Morrison JH, Malenka RC, Nestler EJ (2010) The addicted synapse: mechanisms of synaptic and structural plasticity in nucleus accumbens. Trends Neurosci 33:267–276

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Renthal W, Nestler EJ (2008) Epigenetic mechanisms in drug addiction. Trends Mol Med 14:341–350

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Nestler EJ (2014) Epigenetic mechanisms of drug addiction. Neuropharmacology 76(Pt B):259–268

    CAS  PubMed  Google Scholar 

  14. Fowler CD, Kenny PJ (2011) Intravenous nicotine self-administration and cue-induced reinstatement in mice: effects of nicotine dose, rate of drug infusion and prior instrumental training. Neuropharmacology 61:687–698

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Tuesta LM, Fowler CD, Kenny PJ (2011) Recent advances in understanding nicotinic receptor signaling mechanisms that regulate drug self-administration behavior. Biochem Pharmacol 82:984–995

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Kourrich S, Calu DJ, Bonci A (2015) Intrinsic plasticity: an emerging player in addiction. Nat Rev Neurosci 16:173–184

    CAS  PubMed  Google Scholar 

  17. Caprioli D, Celentano M, Paolone G, Badiani A (2007) Modeling the role of environment in addiction. Prog Neuropsychopharmacol Biol Psychiatry 31:1639–1653

    PubMed  Google Scholar 

  18. Ajonijebu DC, Abboussi O, Russell VA, Mabandla MV, Daniels WMU (2017) Epigenetics: a link between addiction and social environment. Cell Mol Life Sci 74:2735–2747

    CAS  PubMed  Google Scholar 

  19. Moffett MC, Harley J, Francis D, Sanghani SP, Davis WI, Kuhar MJ (2006) Maternal separation and handling affects cocaine self-administration in both the treated pups as adults and the dams. J Pharmacol Exp Ther 317:1210–1218

    CAS  PubMed  Google Scholar 

  20. Robbins TW, Everitt BJ (1996) Neurobehavioural mechanisms of reward and motivation. Curr Opin Neurobiol 6:228–236

    CAS  PubMed  Google Scholar 

  21. Berke JD, Hyman SE (2000) Addiction, dopamine, and the molecular mechanisms of memory. Neuron 25:515–532

    CAS  PubMed  Google Scholar 

  22. Cami J, Farre M (2003) Drug addiction. N Engl J Med 349:975–986

    CAS  PubMed  Google Scholar 

  23. Wise R (1996) Neurobiology of addiction. Curr Opin Neurobiol 6:243–251

    CAS  PubMed  Google Scholar 

  24. Melendez RI, Rodd-Henricks ZA, Engleman EA, Li TK, McBride WJ, Murphy JM (2002) Microdialysis of dopamine in the nucleus accumbens of alcohol-preferring (P) rats during anticipation and operant self-administration of ethanol. Alcohol Clin Exp Res 26:318–325

    CAS  PubMed  Google Scholar 

  25. van Erp AM, Miczek KA (2007) Increased accumbal dopamine during daily alcohol consumption and subsequent aggressive behavior in rats. Psychopharmacology (Berl) 191:679–688

    CAS  Google Scholar 

  26. Fadda P, Scherma M, Spano MS, Salis P, Melis V, Fattore L, Fratta W (2006) Cannabinoid self-administration increases dopamine release in the nucleus accumbens. Neuroreport 17:1629–1632

    CAS  PubMed  Google Scholar 

  27. Lecca D, Cacciapaglia F, Valentini V, Di Chiara G (2006) Monitoring extracellular dopamine in the rat nucleus accumbens shell and core during acquisition and maintenance of intravenous WIN 55,212-2 self-administration. Psychopharmacology (Berl) 188:63–74

    CAS  Google Scholar 

  28. Wise R, Gardner E (2002) Functional anatomy of substance-related disorders. In: D’haenen H, den Boer J, Willner P (eds) Biological psychiatry. Wiley, New York, NY, pp 509–522

    Google Scholar 

  29. O’Brien CP, Gardner EL (2005) Critical assessment of how to study addiction and its treatment: human and non-human animal models. Pharmacol Ther 108:18–58

    PubMed  Google Scholar 

  30. Richardson NR, Smith AM, Roberts DC (1994) A single injection of either flupenthixol decanoate or haloperidol decanoate produces long-term changes in cocaine self-administration in rats. Drug Alcohol Depend 36:23–25

    CAS  PubMed  Google Scholar 

  31. Yokel RA, Wise RA (1975) Increased lever pressing for amphetamine after pimozide in rats: implications for a dopamine theory of reward. Science 187:547–549

    CAS  PubMed  Google Scholar 

  32. Roberts DC, Koob GF (1982) Disruption of cocaine self-administration following 6-hydroxydopamine lesions of the ventral tegmental area in rats. Pharmacol Biochem Behav 17:901–904

    CAS  PubMed  Google Scholar 

  33. Hubner CB, Koob GF (1990) The ventral pallidum plays a role in mediating cocaine and heroin self-administration in the rat. Brain Res 508:20–29

    CAS  PubMed  Google Scholar 

  34. Koob GF (1992) Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci 13:177–184

    CAS  PubMed  Google Scholar 

  35. Koob GF (2003) Neuroadaptive mechanisms of addiction: studies on the extended amygdala. Eur Neuropsychopharmacol 13:442–452

    CAS  PubMed  Google Scholar 

  36. Leith NJ, Barrett RJ (1976) Amphetamine and the reward system: evidence for tolerance and post-drug depression. Psychopharmacologia 46:19–25

    CAS  PubMed  Google Scholar 

  37. Parsons LH, Koob GF, Weiss F (1995) Serotonin dysfunction in the nucleus accumbens of rats during withdrawal after unlimited access to intravenous cocaine. J Pharmacol Exp Ther 274:1182–1191

    CAS  PubMed  Google Scholar 

  38. Markou A, Koob GF (1991) Postcocaine anhedonia. An animal model of cocaine withdrawal. Neuropsychopharmacology 4:17–26

    CAS  PubMed  Google Scholar 

  39. Markou A, Koob GF (1992) Construct validity of a self-stimulation threshold paradigm: effects of reward and performance manipulations. Physiol Behav 51:111–119

    CAS  PubMed  Google Scholar 

  40. Stinus L, Le Moal M, Koob GF (1990) Nucleus accumbens and amygdala are possible substrates for the aversive stimulus effects of opiate withdrawal. Neuroscience 37:767–773

    CAS  PubMed  Google Scholar 

  41. Dahchour A, De Witte P (2000) Taurine blocks the glutamate increase in the nucleus accumbens microdialysate of ethanol-dependent rats. Pharmacol Biochem Behav 65:345–350

    CAS  PubMed  Google Scholar 

  42. Weiss F, Parsons LH, Schulteis G, Hyytia P, Lorang MT, Bloom FE, Koob GF (1996) Ethanol self-administration restores withdrawal-associated deficiencies in accumbal dopamine and 5-hydroxytryptamine release in dependent rats. J Neurosci 16:3474–3485

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Koob GF, Le Moal M (2001) Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology 24:97–129

    CAS  PubMed  Google Scholar 

  44. Koob GF, Le Moal M (1997) Drug abuse: hedonic homeostatic dysregulation. Science 278:52–58

    CAS  PubMed  Google Scholar 

  45. Shaham Y, Shalev U, Lu L, de Wit H, Stewart J (2003) The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology (Berl) 168:3–20

    CAS  Google Scholar 

  46. Stewart J (2000) Pathways to relapse: the neurobiology of drug- and stress-induced relapse to drug-taking. J Psychiatry Neurosci 25:125–136

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Shalev U, Grimm JW, Shaham Y (2002) Neurobiology of relapse to heroin and cocaine seeking: a review. Pharmacol Rev 54:1–42

    CAS  PubMed  Google Scholar 

  48. Boening JA (2001) Neurobiology of an addiction memory. J Neural Transm (Vienna) 108:755–765

    CAS  Google Scholar 

  49. Kilts CD, Gross RE, Ely TD, Drexler KP (2004) The neural correlates of cue-induced craving in cocaine-dependent women. Am J Psychiatry 161:233–241

    PubMed  Google Scholar 

  50. Bonson KR, Grant SJ, Contoreggi CS, Links JM, Metcalfe J, Weyl HL, Kurian V, Ernst M, London ED (2002) Neural systems and cue-induced cocaine craving. Neuropsychopharmacology 26:376–386

    CAS  PubMed  Google Scholar 

  51. Childress AR, Mozley PD, McElgin W, Fitzgerald J, Reivich M, O’Brien CP (1999) Limbic activation during cue-induced cocaine craving. Am J Psychiatry 156:11–18

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Fuchs RA, Feltenstein MW, See RE (2006) The role of the basolateral amygdala in stimulus-reward memory and extinction memory consolidation and in subsequent conditioned cued reinstatement of cocaine seeking. Eur J Neurosci 23:2809–2813

    PubMed  Google Scholar 

  53. Kruzich PJ, See RE (2001) Differential contributions of the basolateral and central amygdala in the acquisition and expression of conditioned relapse to cocaine-seeking behavior. J Neurosci 21:RC155

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Rogers JL, Ghee S, See RE (2008) The neural circuitry underlying reinstatement of heroin-seeking behavior in an animal model of relapse. Neuroscience 151:579–588

    CAS  PubMed  Google Scholar 

  55. McLaughlin J, See RE (2003) Selective inactivation of the dorsomedial prefrontal cortex and the basolateral amygdala attenuates conditioned-cued reinstatement of extinguished cocaine-seeking behavior in rats. Psychopharmacology (Berl) 168:57–65

    CAS  Google Scholar 

  56. Meil WM, See RE (1997) Lesions of the basolateral amygdala abolish the ability of drug associated cues to reinstate responding during withdrawal from self-administered cocaine. Behav Brain Res 87:139–148

    CAS  PubMed  Google Scholar 

  57. Vorel SR, Liu X, Hayes RJ, Spector JA, Gardner EL (2001) Relapse to cocaine-seeking after hippocampal theta burst stimulation. Science 292:1175–1178

    CAS  PubMed  Google Scholar 

  58. Hayes RJ, Vorel SR, Spector J, Liu X, Gardner EL (2003) Electrical and chemical stimulation of the basolateral complex of the amygdala reinstates cocaine-seeking behavior in the rat. Psychopharmacology (Berl) 168:75–83

    CAS  Google Scholar 

  59. Kalivas PW (2004) Glutamate systems in cocaine addiction. Curr Opin Pharmacol 4:23–29

    CAS  PubMed  Google Scholar 

  60. Sinha R (2001) How does stress increase risk of drug abuse and relapse? Psychopharmacology (Berl) 158:343–359

    CAS  Google Scholar 

  61. Shaham Y, Highfield D, Delfs J, Leung S, Stewart J (2000) Clonidine blocks stress-induced reinstatement of heroin seeking in rats: an effect independent of locus coeruleus noradrenergic neurons. Eur J Neurosci 12:292–302

    CAS  PubMed  Google Scholar 

  62. Erb S, Hitchcott PK, Rajabi H, Mueller D, Shaham Y, Stewart J (2000) Alpha-2 adrenergic receptor agonists block stress-induced reinstatement of cocaine seeking. Neuropsychopharmacology 23:138–150

    CAS  PubMed  Google Scholar 

  63. Heinrichs SC, Koob GF (2004) Corticotropin-releasing factor in brain: a role in activation, arousal, and affect regulation. J Pharmacol Exp Ther 311:427–440

    CAS  PubMed  Google Scholar 

  64. Barrot M, Marinelli M, Abrous DN, Rouge-Pont F, Le Moal M, Piazza PV (2000) The dopaminergic hyper-responsiveness of the shell of the nucleus accumbens is hormone-dependent. Eur J Neurosci 12:973–979

    CAS  PubMed  Google Scholar 

  65. Marinelli M, Aouizerate B, Barrot M, Le Moal M, Piazza PV (1998) Dopamine-dependent responses to morphine depend on glucocorticoid receptors. Proc Natl Acad Sci U S A 95:7742–7747

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Saal D, Dong Y, Bonci A, Malenka RC (2003) Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons. Neuron 37:577–582

    CAS  PubMed  Google Scholar 

  67. Gardner E, Ashby C (2000) Heterogeneity of the mesotelencephalic dopamine fibers: physiology and pharmacology. Neurosci Biobehav Rev 24:115–118

    CAS  PubMed  Google Scholar 

  68. Volkow ND, Li TK (2004) Drug addiction: the neurobiology of behaviour gone awry. Nat Rev Neurosci 5:963–970

    CAS  PubMed  Google Scholar 

  69. Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33(Suppl):245–254

    CAS  PubMed  Google Scholar 

  70. Kornberg RD, Lorch Y (1999) Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 98:285–294

    CAS  PubMed  Google Scholar 

  71. Grunstein M (1997) Histone acetylation in chromatin structure and transcription. Nature 389:349–352

    CAS  PubMed  Google Scholar 

  72. Felsenfeld G, Groudine M (2003) Controlling the double helix. Nature 421:448–453

    PubMed  Google Scholar 

  73. Li B, Carey M, Workman JL (2007) The role of chromatin during transcription. Cell 128:707–719

    CAS  PubMed  Google Scholar 

  74. Berger SL (2007) The complex language of chromatin regulation during transcription. Nature 447:407–412

    CAS  PubMed  Google Scholar 

  75. Cheung P, Allis CD, Sassone-Corsi P (2000) Signaling to chromatin through histone modifications. Cell 103:263–271

    CAS  PubMed  Google Scholar 

  76. Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705

    CAS  PubMed  Google Scholar 

  77. Haig D (2004) The (dual) origin of epigenetics. Cold Spring Harb Symp Quant Biol 69:67–70

    CAS  PubMed  Google Scholar 

  78. McQuown SC, Wood MA (2010) Epigenetic regulation in substance use disorders. Curr Psychiatry Rep 12:145–153

    PubMed  PubMed Central  Google Scholar 

  79. Waddington CH (1957) The strategy of the genes: a discussion of some aspects of theoretical biology. Allen & Unwin, Crows Nest, NSW

    Google Scholar 

  80. Morange M (2005) How to localize epigenetics in the landscape of biological research? Med Sci (Paris) 21:367–369

    Google Scholar 

  81. Felsenfeld G (2014) A brief history of epigenetics. Cold Spring Harb Perspect Biol 6:a018200

    PubMed  PubMed Central  Google Scholar 

  82. Day JJ, Sweatt JD (2010) DNA methylation and memory formation. Nat Neurosci 13:1319–1323

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074–1080

    CAS  PubMed  Google Scholar 

  84. Okazaki IJ, Moss J (1999) Characterization of glycosylphosphatidylinositol-anchored, secreted, and intracellular vertebrate mono-ADP-ribosyltransferases. Annu Rev Nutr 19:485–509

    CAS  PubMed  Google Scholar 

  85. Ramoz N, Gorwood P (2015) A genetic view of addiction. Med Sci (Paris) 31:432–438

    Google Scholar 

  86. Robison AJ, Nestler EJ (2011) Transcriptional and epigenetic mechanisms of addiction. Nat Rev Neurosci 12:623–637

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Ray-Gallet D, Gerard A, Polo S, Almouzni G (2005) Variations on the topic of the “histone code”. Med Sci (Paris) 21:384–389

    Google Scholar 

  88. Barrett RM, Wood MA (2008) Beyond transcription factors: the role of chromatin modifying enzymes in regulating transcription required for memory. Learn Mem 15:460–467

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Norton VG, Imai BS, Yau P, Bradbury EM (1989) Histone acetylation reduces nucleosome core particle linking number change. Cell 57:449–457

    CAS  PubMed  Google Scholar 

  90. Kuo MH, Allis CD (1998) Roles of histone acetyltransferases and deacetylases in gene regulation. Bioessays 20:615–626

    CAS  PubMed  Google Scholar 

  91. Narlikar GJ, Fan HY, Kingston RE (2002) Cooperation between complexes that regulate chromatin structure and transcription. Cell 108:475–487

    CAS  PubMed  Google Scholar 

  92. Loidl P (1994) Histone acetylation: facts and questions. Chromosoma 103:441–449

    CAS  PubMed  Google Scholar 

  93. Dokmanovic M, Clarke C, Marks PA (2007) Histone deacetylase inhibitors: overview and perspectives. Mol Cancer Res 5:981–989

    CAS  PubMed  Google Scholar 

  94. Hake SB, Xiao A, Allis CD (2004) Linking the epigenetic ‘language’ of covalent histone modifications to cancer. Br J Cancer 90:761–769

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y (2004) Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell 119:941–953

    CAS  PubMed  Google Scholar 

  96. Tachibana M, Sugimoto K, Fukushima T, Shinkai Y (2001) Set domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3. J Biol Chem 276:25309–25317

    CAS  PubMed  Google Scholar 

  97. Bannister AJ, Kouzarides T (2005) Reversing histone methylation. Nature 436:1103–1106

    CAS  PubMed  Google Scholar 

  98. Rice JC, Allis CD (2001) Histone methylation versus histone acetylation: new insights into epigenetic regulation. Curr Opin Cell Biol 13:263–273

    CAS  PubMed  Google Scholar 

  99. Moore LD, Le T, Fan G (2013) DNA methylation and its basic function. Neuropsychopharmacology 38:23–38

    CAS  PubMed  Google Scholar 

  100. Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM, Song JJ, Hammond SM, Joshua-Tor L, Hannon GJ (2004) Argonaute2 is the catalytic engine of mammalian RNAi. Science 305:1437–1441

    CAS  PubMed  Google Scholar 

  101. Song JJ, Smith SK, Hannon GJ, Joshua-Tor L (2004) Crystal structure of Argonaute and its implications for RISC slicer activity. Science 305:1434–1437

    CAS  PubMed  Google Scholar 

  102. Hansen KF, Sakamoto K, Wayman GA, Impey S, Obrietan K (2010) Transgenic miR132 alters neuronal spine density and impairs novel object recognition memory. PLoS One 5:e15497

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Vo N, Klein ME, Varlamova O, Keller DM, Yamamoto T, Goodman RH, Impey S (2005) A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis. Proc Natl Acad Sci U S A 102:16426–16431

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Bentwich I, Avniel A, Karov Y, Aharonov R, Gilad S, Barad O, Barzilai A, Einat P, Einav U, Meiri E, Sharon E, Spector Y, Bentwich Z (2005) Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 37:766–770

    CAS  PubMed  Google Scholar 

  105. Berezikov E, Thuemmler F, van Laake LW, Kondova I, Bontrop R, Cuppen E, Plasterk RH (2006) Diversity of microRNAs in human and chimpanzee brain. Nat Genet 38:1375–1377

    CAS  PubMed  Google Scholar 

  106. Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V (2004) Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol 5:R13

    PubMed  PubMed Central  Google Scholar 

  107. Lugli G, Torvik VI, Larson J, Smalheiser NR (2008) Expression of microRNAs and their precursors in synaptic fractions of adult mouse forebrain. J Neurochem 106:650–661

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15–20

    CAS  PubMed  Google Scholar 

  109. Friedman RC, Farh KK, Burge CB, Bartel DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19:92–105

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T (2001) Identification of novel genes coding for small expressed RNAs. Science 294:853–858

    CAS  PubMed  Google Scholar 

  111. Lai EC (2002) Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation. Nat Genet 30:363

    CAS  PubMed  Google Scholar 

  112. Vasudevan S, Tong Y, Steitz JA (2007) Switching from repression to activation: microRNAs can up-regulate translation. Science 318:1931–1934

    CAS  PubMed  Google Scholar 

  113. Kung JTY, Colognori D, Lee JT (2013) Long noncoding RNAs: past, present, and future. Genetics 193:651–669

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Rinn JL, Chang HY (2012) Genome regulation by long noncoding RNAs. Annu Rev Biochem 81:145. https://doi.org/10.1146/annurev-biochem-051410-092902

    Article  CAS  PubMed  Google Scholar 

  115. Vance KW, Ponting CP (2014) Transcriptional regulatory functions of nuclear long noncoding RNAs. Trends Genet 30:348–355

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Kalda A, Heidmets LT, Shen HY, Zharkovsky A, Chen JF (2007) Histone deacetylase inhibitors modulates the induction and expression of amphetamine-induced behavioral sensitization partially through an associated learning of the environment in mice. Behav Brain Res 181:76–84

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Kumar A, Choi KH, Renthal W, Tsankova NM, Theobald DE, Truong HT, Russo SJ, Laplant Q, Sasaki TS, Whistler KN, Neve RL, Self DW, Nestler EJ (2005) Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum. Neuron 48:303–314

    CAS  PubMed  Google Scholar 

  118. Schroeder FA, Penta KL, Matevossian A, Jones SR, Konradi C, Tapper AR, Akbarian S (2008) Drug-induced activation of dopamine D(1) receptor signaling and inhibition of class I/II histone deacetylase induce chromatin remodeling in reward circuitry and modulate cocaine-related behaviors. Neuropsychopharmacology 33:2981–2992

    CAS  PubMed  Google Scholar 

  119. Shen HY, Kalda A, Yu L, Ferrara J, Zhu J, Chen JF (2008) Additive effects of histone deacetylase inhibitors and amphetamine on histone H4 acetylation, cAMP responsive element binding protein phosphorylation and DeltaFosB expression in the striatum and locomotor sensitization in mice. Neuroscience 157:644–655

    CAS  PubMed  Google Scholar 

  120. Shibasaki M, Mizuno K, Kurokawa K, Ohkuma S (2011) L-type voltage-dependent calcium channels facilitate acetylation of histone H3 through PKCgamma phosphorylation in mice with methamphetamine-induced place preference. J Neurochem 118:1056–1066

    CAS  PubMed  Google Scholar 

  121. Pandey SC, Zhang H, Ugale R, Prakash A, Xu T, Misra K (2008) Effector immediate-early gene arc in the amygdala plays a critical role in alcoholism. J Neurosci 28:2589–2600

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Renthal W, Nestler EJ (2009) Histone acetylation in drug addiction. Semin Cell Dev Biol 20:387–394

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Renthal W, Maze I, Krishnan V, Covington HE 3rd, Xiao G, Kumar A, Russo SJ, Graham A, Tsankova N, Kippin TE, Kerstetter KA, Neve RL, Haggarty SJ, McKinsey TA, Bassel-Duby R, Olson EN, Nestler EJ (2007) Histone deacetylase 5 epigenetically controls behavioral adaptations to chronic emotional stimuli. Neuron 56:517–529

    CAS  PubMed  Google Scholar 

  124. Wang L, Lv Z, Hu Z, Sheng J, Hui B, Sun J, Ma L (2010) Chronic cocaine-induced H3 acetylation and transcriptional activation of CaMKIIalpha in the nucleus accumbens is critical for motivation for drug reinforcement. Neuropsychopharmacology 35:913–928

    CAS  PubMed  Google Scholar 

  125. Kennedy PJ, Feng J, Robison AJ, Maze I, Badimon A, Mouzon E, Chaudhury D, Damez-Werno DM, Haggarty SJ, Han MH, Bassel-Duby R, Olson EN, Nestler EJ (2013) Class I HDAC inhibition blocks cocaine-induced plasticity by targeted changes in histone methylation. Nat Neurosci 16:434–440

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Malvaez M, McQuown SC, Rogge GA, Astarabadi M, Jacques V, Carreiro S, Rusche JR, Wood MA (2013) HDAC3-selective inhibitor enhances extinction of cocaine-seeking behavior in a persistent manner. Proc Natl Acad Sci U S A 110:2647–2652

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Romieu P, Host L, Gobaille S, Sandner G, Aunis D, Zwiller J (2008) Histone deacetylase inhibitors decrease cocaine but not sucrose self-administration in rats. J Neurosci 28:9342–9348

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Warnault V, Darcq E, Levine A, Barak S, Ron D (2013) Chromatin remodeling--a novel strategy to control excessive alcohol drinking. Transl Psychiatry 3:e231

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Malvaez M, Sanchis-Segura C, Vo D, Lattal KM, Wood MA (2010) Modulation of chromatin modification facilitates extinction of cocaine-induced conditioned place preference. Biol Psychiatry 67:36–43

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Pastor V, Host L, Zwiller J, Bernabeu R (2011) Histone deacetylase inhibition decreases preference without affecting aversion for nicotine. J Neurochem 116:636–645

    CAS  PubMed  Google Scholar 

  131. Legastelois R, Botia B, Naassila M (2013) Blockade of ethanol-induced behavioral sensitization by sodium butyrate: descriptive analysis of gene regulations in the striatum. Alcohol Clin Exp Res 37:1143–1153

    CAS  PubMed  Google Scholar 

  132. Romieu P, Deschatrettes E, Host L, Gobaille S, Sandner G, Zwiller J (2011) The inhibition of histone deacetylases reduces the reinstatement of cocaine-seeking behavior in rats. Curr Neuropharmacol 9:21–25

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Sun J, Wang L, Jiang B, Hui B, Lv Z, Ma L (2008) The effects of sodium butyrate, an inhibitor of histone deacetylase, on the cocaine- and sucrose-maintained self-administration in rats. Neurosci Lett 441:72–76

    CAS  PubMed  Google Scholar 

  134. Sanchis-Segura C, Lopez-Atalaya JP, Barco A (2009) Selective boosting of transcriptional and behavioral responses to drugs of abuse by histone deacetylase inhibition. Neuropsychopharmacology 34:2642–2654

    CAS  PubMed  Google Scholar 

  135. Ikegami D, Narita M, Imai S, Miyashita K, Tamura R, Narita M, Takagi S, Yokomizo A, Takeshima H, Ando T, Igarashi K, Kanno J, Kuzumaki N, Ushijima T, Suzuki T (2010) Epigenetic modulation at the CCR2 gene correlates with the maintenance of behavioral sensitization to methamphetamine. Addict Biol 15:358–361

    CAS  PubMed  Google Scholar 

  136. Aguilar-Valles A, Vaissiere T, Griggs EM, Mikaelsson MA, Takacs IF, Young EJ, Rumbaugh G, Miller CA (2014) Methamphetamine-associated memory is regulated by a writer and an eraser of permissive histone methylation. Biol Psychiatry 76:57–65

    CAS  PubMed  Google Scholar 

  137. Maze I, Covington HE III, Dietz DM, LaPlant Q, Renthal W, Russo SJ, Mechanic M, Mouzon E, Neve RL, Haggarty SJ, Ren Y, Sampath SC, Hurd YL, Greengard P, Tarakhovsky A, Schaefer A, Nestler EJ (2010) Essential role of the histone methyltransferase G9a in cocaine-induced plasticity. Science 327:213–216

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Sun H, Maze I, Dietz DM, Scobie KN, Kennedy PJ, Damez-Werno D, Neve RL, Zachariou V, Shen L, Nestler EJ (2012) Morphine epigenomically regulates behavior through alterations in histone H3 lysine 9 dimethylation in the nucleus accumbens. J Neurosci 32:17454–17464

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Feng J, Nestler EJ (2013) Epigenetic mechanisms of drug addiction. Curr Opin Neurobiol 23:521–528

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Kelz MB, Chen J, Carlezon WA Jr, Whisler K, Gilden L, Beckmann AM, Steffen C, Zhang YJ, Marotti L, Self DW, Tkatch T, Baranauskas G, Surmeier DJ, Neve RL, Duman RS, Picciotto MR, Nestler EJ (1999) Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine. Nature 401:272–276

    CAS  PubMed  Google Scholar 

  141. Zachariou V, Bolanos CA, Selley DE, Theobald D, Cassidy MP, Kelz MB, Shaw-Lutchman T, Berton O, Sim-Selley LJ, Dileone RJ, Kumar A, Nestler EJ (2006) An essential role for DeltaFosB in the nucleus accumbens in morphine action. Nat Neurosci 9:205–211

    CAS  PubMed  Google Scholar 

  142. Colby CR, Whisler K, Steffen C, Nestler EJ, Self DW (2003) Striatal cell type-specific overexpression of DeltaFosB enhances incentive for cocaine. J Neurosci 23:2488–2493

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Feng W, Bachant J, Collingwood D, Raghuraman MK, Brewer BJ (2009) Centromere replication timing determines different forms of genomic instability in Saccharomyces cerevisiae checkpoint mutants during replication stress. Genetics 183:1249–1260

    CAS  PubMed  PubMed Central  Google Scholar 

  144. LaPlant Q, Vialou V, Covington HE III, Dumitriu D, Feng J, Warren BL, Maze I, Dietz DM, Watts EL, Iniguez SD, Koo JW, Mouzon E, Renthal W, Hollis F, Wang H, Noonan MA, Ren Y, Eisch AJ, Bolanos CA, Kabbaj M, Xiao G, Neve RL, Hurd YL, Oosting RS, Fan G, Morrison JH, Nestler EJ (2010) Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens. Nat Neurosci 13:1137–1143

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Anier K, Zharkovsky A, Kalda A (2013) S-adenosylmethionine modifies cocaine-induced DNA methylation and increases locomotor sensitization in mice. Int J Neuropsychopharmacol 16:2053–2066

    CAS  PubMed  Google Scholar 

  146. Tian W, Zhao M, Li M, Song T, Zhang M, Quan L, Li S, Sun ZS (2012) Reversal of cocaine-conditioned place preference through methyl supplementation in mice: altering global DNA methylation in the prefrontal cortex. PLoS One 7:e33435

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Im HI, Hollander JA, Bali P, Kenny PJ (2010) MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212. Nat Neurosci 13:1120–1127

    CAS  PubMed  PubMed Central  Google Scholar 

  148. He Y, Yang C, Kirkmire CM, Wang ZJ (2010) Regulation of opioid tolerance by let-7 family microRNA targeting the mu opioid receptor. J Neurosci 30:10251–10258

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Moonat S, Sakharkar AJ, Zhang H, Pandey SC (2011) The role of amygdaloid brain-derived neurotrophic factor, activity-regulated cytoskeleton-associated protein and dendritic spines in anxiety and alcoholism. Addict Biol 16:238–250

    CAS  PubMed  Google Scholar 

  150. Deng JV, Rodriguiz RM, Hutchinson AN, Kim IH, Wetsel WC, West AE (2010) MeCP2 in the nucleus accumbens contributes to neural and behavioral responses to psychostimulants. Nat Neurosci 13:1128–1136

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Wright KN, Hollis F, Duclot F, Dossat AM, Strong CE, Francis TC, Mercer R, Feng J, Dietz DM, Lobo MK, Nestler EJ, Kabbaj M (2015) Methyl supplementation attenuates cocaine-seeking behaviors and cocaine-induced c-Fos activation in a DNA methylation-dependent manner. J Neurosci 35:8948–8958

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Feng J, Shao N, Szulwach KE, Vialou V, Huynh J, Zhong C, Le T, Ferguson D, Cahill ME, Li Y, Koo JW, Ribeiro E, Labonte B, Laitman BM, Estey D, Stockman V, Kennedy P, Courousse T, Mensah I, Turecki G, Faull KF, Ming GL, Song H, Fan G, Casaccia P, Shen L, Jin P, Nestler EJ (2015) Role of Tet1 and 5-hydroxymethylcytosine in cocaine action. Nat Neurosci 18:536–544

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Vinken K, Vogels R (2017) Adaptation can explain evidence for encoding of probabilistic information in macaque inferior temporal cortex. Curr Biol 27:R1210–R1212

    CAS  PubMed  Google Scholar 

  154. Takahashi K, Yokota S, Tatsumi N, Fukami T, Yokoi T, Nakajima M (2013) Cigarette smoking substantially alters plasma microRNA profiles in healthy subjects. Toxicol Appl Pharmacol 272:154–160

    CAS  PubMed  Google Scholar 

  155. Banerjee A, Waters D, Camacho OM, Minet E (2015) Quantification of plasma microRNAs in a group of healthy smokers, ex-smokers and non-smokers and correlation to biomarkers of tobacco exposure. Biomarkers 20:123–131

    CAS  PubMed  PubMed Central  Google Scholar 

  156. McCrae JC, Sharkey N, Webb DJ, Vliegenthart AD, Dear JW (2016) Ethanol consumption produces a small increase in circulating miR-122 in healthy individuals. Clin Toxicol (Phila) 54:53–55

    CAS  Google Scholar 

  157. Zhao Y, Zhang K, Jiang H, Du J, Na Z, Hao W, Yu S, Zhao M (2016) Decreased expression of plasma microRNA in patients with methamphetamine (MA) use disorder. J Neuroimmune Pharmacol 11:542–548

    PubMed  Google Scholar 

  158. Hyman SE (2005) Addiction: a disease of learning and memory. Am J Psychiatry 162:1414–1422

    PubMed  Google Scholar 

  159. Luscher C, Malenka RC (2011) Drug-evoked synaptic plasticity in addiction: from molecular changes to circuit remodeling. Neuron 69:650–663

    PubMed  PubMed Central  Google Scholar 

  160. Mameli M, Bellone C, Brown MT, Luscher C (2011) Cocaine inverts rules for synaptic plasticity of glutamate transmission in the ventral tegmental area. Nat Neurosci 14:414–416

    CAS  PubMed  Google Scholar 

  161. Dreyer JL (2010) New insights into the roles of microRNAs in drug addiction and neuroplasticity. Genome Med 2:92

    CAS  PubMed  PubMed Central  Google Scholar 

  162. Pietrzykowski AZ (2010) The role of microRNAs in drug addiction: a big lesson from tiny molecules. Int Rev Neurobiol 91:1–24

    CAS  PubMed  Google Scholar 

  163. Li MD, van der Vaart AD (2011) MicroRNAs in addiction: adaptation’s middlemen? Mol Psychiatry 16:1159–1168

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Hollander JA, Im HI, Amelio AL, Kocerha J, Bali P, Lu Q, Willoughby D, Wahlestedt C, Conkright MD, Kenny PJ (2010) Striatal microRNA controls cocaine intake through CREB signalling. Nature 466:197–202

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Sadakierska-Chudy A, Frankowska M, Miszkiel J, Wydra K, Jastrzebska J, Filip M (2017) Prolonged induction of miR-212/132 and REST expression in rat striatum following cocaine self-administration. Mol Neurobiol 54:2241–2254

    CAS  PubMed  Google Scholar 

  166. Carlezon WA Jr, Thome J, Olson VG, Lane-Ladd SB, Brodkin ES, Hiroi N, Duman RS, Neve RL, Nestler EJ (1998) Regulation of cocaine reward by CREB. Science 282:2272–2275

    CAS  PubMed  Google Scholar 

  167. Dinieri JA, Nemeth CL, Parsegian A, Carle T, Gurevich VV, Gurevich E, Neve RL, Nestler EJ, Carlezon WA Jr (2009) Altered sensitivity to rewarding and aversive drugs in mice with inducible disruption of cAMP response element-binding protein function within the nucleus accumbens. J Neurosci 29:1855–1859

    CAS  PubMed  PubMed Central  Google Scholar 

  168. McClung CA, Nestler EJ (2003) Regulation of gene expression and cocaine reward by CREB and DeltaFosB. Nat Neurosci 6:1208–1215

    CAS  PubMed  Google Scholar 

  169. Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, Bird A (1998) Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393:386–389

    CAS  PubMed  Google Scholar 

  170. Chandrasekar V, Dreyer JL (2009) microRNAs miR-124, let-7d and miR-181a regulate cocaine-induced plasticity. Mol Cell Neurosci 42:350–362

    CAS  PubMed  Google Scholar 

  171. Chandrasekar V, Dreyer JL (2011) 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

    CAS  PubMed  PubMed Central  Google Scholar 

  172. Schaefer A, Im HI, Veno MT, Fowler CD, Min A, Intrator A, Kjems J, Kenny PJ, O’Carroll D, Greengard P (2010) Argonaute 2 in dopamine 2 receptor-expressing neurons regulates cocaine addiction. J Exp Med 207:1843–1851

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Sartor GC, St Laurent G 3rd, Wahlestedt C (2012) The emerging role of non-coding RNAs in drug addiction. Front Genet 3:106

    CAS  PubMed  PubMed Central  Google Scholar 

  174. Mattson ME, Lynch S (2013) Medication prescribing and behavioral treatment for substance use disorders in physician office settings. In: The CBHSQ report. CBHSQ, Rockville, MD, pp 1–6

    Google Scholar 

  175. Di Chiara G (2002) Nucleus accumbens shell and core dopamine: differential role in behavior and addiction. Behav Brain Res 137:75–114

    PubMed  Google Scholar 

  176. Volkow ND, Fowler JS, Wang GJ (2003) The addicted human brain: insights from imaging studies. J Clin Invest 111:1444–1451

    CAS  PubMed  PubMed Central  Google Scholar 

  177. Volkow ND, Fowler JS, Wang GJ, Hitzemann R, Logan J, Schlyer DJ, Dewey SL, Wolf AP (1993) Decreased dopamine D2 receptor availability is associated with reduced frontal metabolism in cocaine abusers. Synapse 14:169–177

    CAS  PubMed  Google Scholar 

  178. See RE (2005) Neural substrates of cocaine-cue associations that trigger relapse. Eur J Pharmacol 526:140–146

    CAS  PubMed  Google Scholar 

  179. Chawla S, Vanhoutte P, Arnold FJ, Huang CL, Bading H (2003) Neuronal activity-dependent nucleocytoplasmic shuttling of HDAC4 and HDAC5. J Neurochem 85:151–159

    CAS  PubMed  Google Scholar 

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Beayno, A., El Hayek, S., Noufi, P., Tarabay, Y., Shamseddeen, W. (2019). The Role of Epigenetics in Addiction: Clinical Overview and Recent Updates. In: Kobeissy, F. (eds) Psychiatric Disorders. Methods in Molecular Biology, vol 2011. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9554-7_35

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