pp 1-29 | Cite as

Transcriptional Regulators as Targets for Alcohol Pharmacotherapies

Chapter
Part of the Handbook of Experimental Pharmacology book series

Abstract

Alcohol use disorder (AUD) is a chronic relapsing brain disease that currently afflicts over 15 million adults in the United States. Despite its prevalence, there are only three FDA-approved medications for AUD treatment, all of which show limited efficacy. Because of their ability to alter expression of a large number of genes, often with great cell-type and brain-region specificity, transcription factors and epigenetic modifiers serve as promising new targets for the development of AUD treatments aimed at the neural circuitry that underlies chronic alcohol abuse. In this chapter, we will discuss transcriptional regulators that can be targeted pharmacologically and have shown some efficacy in attenuating alcohol consumption when targeted. Specifically, the transcription factors cyclic AMP-responsive element binding protein (CREB), peroxisome proliferator-activated receptors (PPARs), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and glucocorticoid receptor (GR), as well as the epigenetic enzymes, the DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), will be discussed.

Keywords

CREB DNA methylation DNA methyltransferase DNMT Glucocorticoid receptor HDAC Histone acetylation Histone deacetylase Nuclear factor kappa B PPAR 

Notes

Acknowledgements

A.W.L. is supported by the National Institute on Alcohol Abuse and Alcoholism (INIA U01 AA020912 and the Center for Alcohol Research in Epigenetics P50 AA022538).

References

  1. Al Ameri M, Al Mansouri S, Al Maamari A, Bahi A (2014) The histone deacetylase (HDAC) inhibitor valproic acid reduces ethanol consumption and ethanol-conditioned place preference in rats. Brain Res 1583:122–131.  https://doi.org/10.1016/j.brainres.2014.07.051CrossRefPubMedGoogle Scholar
  2. Aleshin S, Strokin M, Sergeeva M, Reiser G (2013) Peroxisome proliferator-activated receptor (PPAR)beta/delta, a possible nexus of PPARalpha- and PPARgamma-dependent molecular pathways in neurodegenerative diseases: review and novel hypotheses. Neurochem Int 63(4):322–330.  https://doi.org/10.1016/j.neuint.2013.06.012CrossRefPubMedGoogle Scholar
  3. Arora DS, Nimitvilai S, Teppen TL, McElvain MA, Sakharkar AJ, You C, Pandey SC, Brodie MS (2013) Hyposensitivity to gamma-aminobutyric acid in the ventral tegmental area during alcohol withdrawal: reversal by histone deacetylase inhibitors. Neuropsychopharmacology 38(9):1674–1684.  https://doi.org/10.1038/npp.2013.65CrossRefPubMedPubMedCentralGoogle Scholar
  4. Asher O, Cunningham TD, Yao L, Gordon AS, Diamond I (2002) Ethanol stimulates cAMP-responsive element (CRE)-mediated transcription via CRE-binding protein and cAMP-dependent protein kinase. J Pharmacol Exp Ther 301(1):66–70CrossRefPubMedGoogle Scholar
  5. Auta J, Zhang H, Pandey SC, Guidotti A (2017) Chronic alcohol exposure differentially alters one-carbon metabolism in rat liver and brain. Alcohol Clin Exp Res 41(6):1105–1111.  https://doi.org/10.1111/acer.13382CrossRefPubMedGoogle Scholar
  6. Barbier E, Tapocik JD, Juergens N, Pitcairn C, Borich A, Schank JR, Sun H, Schuebel K, Zhou Z, Yuan Q, Vendruscolo LF, Goldman D, Heilig M (2015) DNA methylation in the medial prefrontal cortex regulates alcohol-induced behavior and plasticity. J Neurosci 35(15):6153–6164.  https://doi.org/10.1523/JNEUROSCI.4571-14.2015CrossRefPubMedPubMedCentralGoogle Scholar
  7. Barson JR, Karatayev O, Chang GQ, Johnson DF, Bocarsly ME, Hoebel BG, Leibowitz SF (2009) Positive relationship between dietary fat, ethanol intake, triglycerides, and hypothalamic peptides: counteraction by lipid-lowering drugs. Alcohol 43(6):433–441.  https://doi.org/10.1016/j.alcohol.2009.07.003CrossRefPubMedPubMedCentralGoogle Scholar
  8. Bell RL, Lopez MF, Cui C, Egli M, Johnson KW, Franklin KM, Becker HC (2015) Ibudilast reduces alcohol drinking in multiple animal models of alcohol dependence. Addict Biol 20(1):38–42.  https://doi.org/10.1111/adb.12106CrossRefPubMedGoogle Scholar
  9. Berger J, Moller DE (2002) The mechanisms of action of PPARs. Annu Rev Med 53:409–435.  https://doi.org/10.1146/annurev.med.53.082901.104018CrossRefPubMedGoogle Scholar
  10. Blednov YA, Benavidez JM, Black M, Harris RA (2014) Inhibition of phosphodiesterase 4 reduces ethanol intake and preference in C57BL/6J mice. Front Neurosci 8:129.  https://doi.org/10.3389/fnins.2014.00129CrossRefPubMedPubMedCentralGoogle Scholar
  11. Blednov YA, Benavidez JM, Black M, Ferguson LB, Schoenhard GL, Goate AM, Edenberg HJ, Wetherill L, Hesselbrock V, Foroud T, Harris RA (2015) Peroxisome proliferator-activated receptors alpha and gamma are linked with alcohol consumption in mice and withdrawal and dependence in humans. Alcohol Clin Exp Res 39(1):136–145.  https://doi.org/10.1111/acer.12610CrossRefPubMedGoogle Scholar
  12. Blednov YA, Black M, Benavidez JM, Stamatakis EE, Harris RA (2016) PPAR agonists: I. Role of receptor subunits in alcohol consumption in male and female mice. Alcohol Clin Exp Res 40(3):553–562.  https://doi.org/10.1111/acer.12976CrossRefPubMedPubMedCentralGoogle Scholar
  13. Bleich S, Lenz B, Ziegenbein M, Beutler S, Frieling H, Kornhuber J, Bonsch D (2006) Epigenetic DNA hypermethylation of the HERP gene promoter induces down-regulation of its mRNA expression in patients with alcohol dependence. Alcohol Clin Exp Res 30(4):587–591.  https://doi.org/10.1111/j.1530-0277.2006.00068.xCrossRefPubMedGoogle Scholar
  14. Bohnsack JP, Patel VK, Morrow AL (2017) Ethanol exposure regulates Gabra1 expression via histone deacetylation at the promoter in cultured cortical neurons. J Pharmacol Exp Ther 363(1):1–11.  https://doi.org/10.1124/jpet.117.242446CrossRefPubMedGoogle Scholar
  15. Bonsch D, Lenz B, Reulbach U, Kornhuber J, Bleich S (2004) Homocysteine associated genomic DNA hypermethylation in patients with chronic alcoholism. J Neural Transm (Vienna) 111(12):1611–1616.  https://doi.org/10.1007/s00702-004-0232-xCrossRefGoogle Scholar
  16. Bonsch D, Lenz B, Kornhuber J, Bleich S (2005) DNA hypermethylation of the alpha synuclein promoter in patients with alcoholism. Neuroreport 16(2):167–170CrossRefPubMedGoogle Scholar
  17. Bonsch D, Lenz B, Fiszer R, Frieling H, Kornhuber J, Bleich S (2006) Lowered DNA methyltransferase (DNMT-3b) mRNA expression is associated with genomic DNA hypermethylation in patients with chronic alcoholism. J Neural Transm (Vienna) 113(9):1299–1304.  https://doi.org/10.1007/s00702-005-0413-2CrossRefGoogle Scholar
  18. Botia B, Legastelois R, Alaux-Cantin S, Naassila M (2012) Expression of ethanol-induced behavioral sensitization is associated with alteration of chromatin remodeling in mice. PLoS One 7(10):e47527.  https://doi.org/10.1371/journal.pone.0047527ADSCrossRefPubMedPubMedCentralGoogle Scholar
  19. Brown SA, Vik PW, Patterson TL, Grant I, Schuckit MA (1995) Stress, vulnerability and adult alcohol relapse. J Stud Alcohol 56(5):538–545CrossRefPubMedGoogle Scholar
  20. Bruckmann C, Islam SA, MacIsaac JL, Morin AM, Karle KN, Di Santo A, Wust R, Lang I, Batra A, Kobor MS, Nieratschker V (2017) DNA methylation signatures of chronic alcohol dependence in purified CD3(+) T-cells of patients undergoing alcohol treatment. Sci Rep 7(1):6605.  https://doi.org/10.1038/s41598-017-06847-zADSCrossRefPubMedPubMedCentralGoogle Scholar
  21. Cervera-Juanes R, Wilhelm LJ, Park B, Grant KA, Ferguson B (2017a) Alcohol-dose-dependent DNA methylation and expression in the nucleus accumbens identifies coordinated regulation of synaptic genes. Transl Psychiatry 7(1):e994.  https://doi.org/10.1038/tp.2016.266CrossRefPubMedPubMedCentralGoogle Scholar
  22. Cervera-Juanes R, Wilhelm LJ, Park B, Grant KA, Ferguson B (2017b) Genome-wide analysis of the nucleus accumbens identifies DNA methylation signals differentiating low/binge from heavy alcohol drinking. Alcohol 60:103–113.  https://doi.org/10.1016/j.alcohol.2016.11.003CrossRefPubMedGoogle Scholar
  23. Chen J, Hutchison KE, Calhoun VD, Claus ED, Turner JA, Sui J, Liu J (2015) CREB-BDNF pathway influences alcohol cue-elicited activation in drinkers. Hum Brain Mapp 36(8):3007–3019.  https://doi.org/10.1002/hbm.22824CrossRefPubMedPubMedCentralGoogle Scholar
  24. Cippitelli A, Damadzic R, Hamelink C, Brunnquell M, Thorsell A, Heilig M, Eskay RL (2014) Binge-like ethanol consumption increases corticosterone levels and neurodegeneration whereas occupancy of type II glucocorticoid receptors with mifepristone is neuroprotective. Addict Biol 19(1):27–36.  https://doi.org/10.1111/j.1369-1600.2012.00451.xCrossRefPubMedGoogle Scholar
  25. Clark SL, Aberg KA, Nerella S, Kumar G, McClay JL, Chen W, Xie LY, Harada A, Shabalin AA, Gao G, Bergen SE, Hultman CM, Magnusson PK, Sullivan PF, van den Oord EJ (2015) Combined whole methylome and genomewide association study implicates CNTN4 in alcohol use. Alcohol Clin Exp Res 39(8):1396–1405.  https://doi.org/10.1111/acer.12790CrossRefPubMedPubMedCentralGoogle Scholar
  26. Crews F, Nixon K, Kim D, Joseph J, Shukitt-Hale B, Qin L, Zou J (2006) BHT blocks NF-kappaB activation and ethanol-induced brain damage. Alcohol Clin Exp Res 30(11):1938–1949.  https://doi.org/10.1111/j.1530-0277.2006.00239.xCrossRefPubMedGoogle Scholar
  27. Crews FT, Lawrimore CJ, Walter TJ, Coleman LG Jr (2017) The role of neuroimmune signaling in alcoholism. Neuropharmacology 122:56–73.  https://doi.org/10.1016/j.neuropharm.2017.01.031CrossRefPubMedGoogle Scholar
  28. Cuevas-Ramos D, Lim DST, Fleseriu M (2016) Update on medical treatment for Cushing’s disease. Clin Diabetes Endocrinol 2:16.  https://doi.org/10.1186/s40842-016-0033-9CrossRefPubMedPubMedCentralGoogle Scholar
  29. D’Addario C, Caputi FF, Ekstrom TJ, Di Benedetto M, Maccarrone M, Romualdi P, Candeletti S (2013) Ethanol induces epigenetic modulation of prodynorphin and pronociceptin gene expression in the rat amygdala complex. J Mol Neurosci 49(2):312–319.  https://doi.org/10.1007/s12031-012-9829-yCrossRefPubMedGoogle Scholar
  30. D’Addario C, Shchetynsky K, Pucci M, Cifani C, Gunnar A, Vukojevic V, Padyukov L, Terenius L (2017) Genetic variation and epigenetic modification of the prodynorphin gene in peripheral blood cells in alcoholism. Prog Neuropsychopharmacol Biol Psychiatry 76:195–203.  https://doi.org/10.1016/j.pnpbp.2017.03.012CrossRefPubMedGoogle Scholar
  31. Day JJ, Kennedy AJ, Sweatt JD (2015) DNA methylation and its implications and accessibility for neuropsychiatric therapeutics. Annu Rev Pharmacol Toxicol 55:591–611.  https://doi.org/10.1146/annurev-pharmtox-010814-124527CrossRefPubMedGoogle Scholar
  32. Desrivieres S, Lourdusamy A, Muller C, Ducci F, Wong CP, Kaakinen M, Pouta A, Hartikainen AL, Isohanni M, Charoen P, Peltonen L, Freimer N, Elliott P, Jarvelin MR, Schumann G (2011) Glucocorticoid receptor (NR3C1) gene polymorphisms and onset of alcohol abuse in adolescents. Addict Biol 16(3):510–513.  https://doi.org/10.1111/j.1369-1600.2010.00239.xCrossRefPubMedGoogle Scholar
  33. Dominguez G, Dagnas M, Decorte L, Vandesquille M, Belzung C, Beracochea D, Mons N (2016) Rescuing prefrontal cAMP-CREB pathway reverses working memory deficits during withdrawal from prolonged alcohol exposure. Brain Struct Funct 221(2):865–877.  https://doi.org/10.1007/s00429-014-0941-3CrossRefPubMedGoogle Scholar
  34. Drew PD, Johnson JW, Douglas JC, Phelan KD, Kane CJ (2015) Pioglitazone blocks ethanol induction of microglial activation and immune responses in the hippocampus, cerebellum, and cerebral cortex in a mouse model of fetal alcohol spectrum disorders. Alcohol Clin Exp Res 39(3):445–454.  https://doi.org/10.1111/acer.12639CrossRefPubMedPubMedCentralGoogle Scholar
  35. Edenberg HJ, Xuei X, Wetherill LF, Bierut L, Bucholz K, Dick DM, Hesselbrock V, Kuperman S, Porjesz B, Schuckit MA, Tischfield JA, Almasy LA, Nurnberger JI Jr, Foroud T (2008) Association of NFKB1, which encodes a subunit of the transcription factor NF-kappaB, with alcohol dependence. Hum Mol Genet 17(7):963–970.  https://doi.org/10.1093/hmg/ddm368CrossRefPubMedGoogle Scholar
  36. Elvir L, Duclot F, Wang Z, Kabbaj M (2017) Epigenetic regulation of motivated behaviors by histone deacetylase inhibitors. Neurosci Biobehav Rev.  https://doi.org/10.1016/j.neubiorev.2017.09.030
  37. Fahlke C, Lorenz JG, Long J, Champoux M, Suomi SJ, Higley JD (2000) Rearing experiences and stress-induced plasma cortisol as early risk factors for excessive alcohol consumption in nonhuman primates. Alcohol Clin Exp Res 24(5):644–650CrossRefPubMedGoogle Scholar
  38. Ferguson LB, Most D, Blednov YA, Harris RA (2014) PPAR agonists regulate brain gene expression: relationship to their effects on ethanol consumption. Neuropharmacology 86:397–407.  https://doi.org/10.1016/j.neuropharm.2014.06.024CrossRefPubMedPubMedCentralGoogle Scholar
  39. Finegersh A, Homanics GE (2014) Acute ethanol alters multiple histone modifications at model gene promoters in the cerebral cortex. Alcohol Clin Exp Res 38(7):1865–1873.  https://doi.org/10.1111/acer.12465CrossRefPubMedPubMedCentralGoogle Scholar
  40. Finegersh A, Ferguson C, Maxwell S, Mazariegos D, Farrell D, Homanics GE (2015) Repeated vapor ethanol exposure induces transient histone modifications in the brain that are modified by genotype and brain region. Front Mol Neurosci 8:39.  https://doi.org/10.3389/fnmol.2015.00039CrossRefPubMedPubMedCentralGoogle Scholar
  41. Flores-Bastias O, Karahanian E (2018) Neuroinflammation produced by heavy alcohol intake is due to loops of interactions between Toll-like 4 and TNF receptors, peroxisome proliferator-activated receptors and the central melanocortin system: a novel hypothesis and new therapeutic avenues. Neuropharmacology 128:401–407.  https://doi.org/10.1016/j.neuropharm.2017.11.003CrossRefPubMedGoogle Scholar
  42. Forero DA, Lopez-Leon S, Shin HD, Park BL, Kim DJ (2015) Meta-analysis of six genes (BDNF, DRD1, DRD3, DRD4, GRIN2B and MAOA) involved in neuroplasticity and the risk for alcohol dependence. Drug Alcohol Depend 149:259–263.  https://doi.org/10.1016/j.drugalcdep.2015.01.017CrossRefPubMedGoogle Scholar
  43. Franklin KM, Hauser SR, Lasek AW, McClintick J, Ding ZM, McBride WJ, Bell RL (2015) Reduction of alcohol drinking of alcohol-preferring (P) and high-alcohol drinking (HAD1) rats by targeting phosphodiesterase-4 (PDE4). Psychopharmacology (Berl) 232(13):2251–2262.  https://doi.org/10.1007/s00213-014-3852-3CrossRefGoogle Scholar
  44. Gatta E, Auta J, Gavin DP, Bhaumik DK, Grayson DR, Pandey SC, Guidotti A (2017) Emerging role of one-carbon metabolism and DNA methylation enrichment on delta-containing GABAA receptor expression in the cerebellum of subjects with alcohol use disorders (AUD). Int J Neuropsychopharmacol.  https://doi.org/10.1093/ijnp/pyx075
  45. Gnyszka A, Jastrzebski Z, Flis S (2013) DNA methyltransferase inhibitors and their emerging role in epigenetic therapy of cancer. Anticancer Res 33(8):2989–2996PubMedGoogle Scholar
  46. Greenwald MK, Steinmiller CL, Sliwerska E, Lundahl L, Burmeister M (2013) BDNF Val(66)Met genotype is associated with drug-seeking phenotypes in heroin-dependent individuals: a pilot study. Addict Biol 18(5):836–845.  https://doi.org/10.1111/j.1369-1600.2011.00431.xCrossRefPubMedGoogle Scholar
  47. Guan H, Hou S, Ricciardi RP (2005) DNA binding of repressor nuclear factor-kappaB p50/p50 depends on phosphorylation of Ser337 by the protein kinase A catalytic subunit. J Biol Chem 280(11):9957–9962.  https://doi.org/10.1074/jbc.M412180200CrossRefPubMedGoogle Scholar
  48. Guerrini L, Blasi F, Denis-Donini S (1995) Synaptic activation of NF-kappa B by glutamate in cerebellar granule neurons in vitro. Proc Natl Acad Sci U S A 92(20):9077–9081ADSCrossRefPubMedPubMedCentralGoogle Scholar
  49. Haberland M, Montgomery RL, Olson EN (2009) The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat Rev Genet 10(1):32–42.  https://doi.org/10.1038/nrg2485CrossRefPubMedPubMedCentralGoogle Scholar
  50. Hagerty SL, Bidwell LC, Harlaar N, Hutchison KE (2016) An exploratory association study of alcohol use disorder and DNA methylation. Alcohol Clin Exp Res 40(8):1633–1640.  https://doi.org/10.1111/acer.13138CrossRefPubMedPubMedCentralGoogle Scholar
  51. Hou YN, Vlaskovska M, Cebers G, Kasakov L, Liljequist S, Terenius L (1996) A mu-receptor opioid agonist induces AP-1 and NF-kappa B transcription factor activity in primary cultures of rat cortical neurons. Neurosci Lett 212(3):159–162CrossRefPubMedGoogle Scholar
  52. Hu W, Lu T, Chen A, Huang Y, Hansen R, Chandler LJ, Zhang HT (2011) Inhibition of phosphodiesterase-4 decreases ethanol intake in mice. Psychopharmacology (Berl) 218(2):331–339.  https://doi.org/10.1007/s00213-011-2290-8CrossRefGoogle Scholar
  53. Hu S, Cao Q, Xu P, Ji W, Wang G, Zhang Y (2016) Rolipram stimulates angiogenesis and attenuates neuronal apoptosis through the cAMP/cAMP-responsive element binding protein pathway following ischemic stroke in rats. Exp Ther Med 11(3):1005–1010.  https://doi.org/10.3892/etm.2015.2958CrossRefPubMedGoogle Scholar
  54. Jacquot C, Croft AP, Prendergast MA, Mulholland P, Shaw SG, Little HJ (2008) Effects of the glucocorticoid antagonist, mifepristone, on the consequences of withdrawal from long term alcohol consumption. Alcohol Clin Exp Res 32(12):2107–2116.  https://doi.org/10.1111/j.1530-0277.2008.00799.xCrossRefPubMedGoogle Scholar
  55. Jeanblanc J, Lemoine S, Jeanblanc V, Alaux-Cantin S, Naassila M (2015) The class I-specific HDAC inhibitor MS-275 decreases motivation to consume alcohol and relapse in heavy drinking rats. Int J Neuropsychopharmacol 18(9).  https://doi.org/10.1093/ijnp/pyv029
  56. Joels M, Sarabdjitsingh RA, Karst H (2012) Unraveling the time domains of corticosteroid hormone influences on brain activity: rapid, slow, and chronic modes. Pharmacol Rev 64(4):901–938.  https://doi.org/10.1124/pr.112.005892CrossRefPubMedGoogle Scholar
  57. Kane CJ, Phelan KD, Han L, Smith RR, Xie J, Douglas JC, Drew PD (2011) Protection of neurons and microglia against ethanol in a mouse model of fetal alcohol spectrum disorders by peroxisome proliferator-activated receptor-gamma agonists. Brain Behav Immun 25(Suppl 1):S137–S145.  https://doi.org/10.1016/j.bbi.2011.02.016CrossRefPubMedPubMedCentralGoogle Scholar
  58. Kapur A, Angomchanu R, Dey M (2016) Efficacy of use of long-term, low-dose mifepristone for the treatment of fibroids. J Obstet Gynaecol India 66(Suppl 1):494–498.  https://doi.org/10.1007/s13224-016-0861-7CrossRefPubMedPubMedCentralGoogle Scholar
  59. Karahanian E, Quintanilla ME, Fernandez K, Israel Y (2014) Fenofibrate – a lipid-lowering drug – reduces voluntary alcohol drinking in rats. Alcohol 48(7):665–670.  https://doi.org/10.1016/j.alcohol.2014.08.004CrossRefPubMedGoogle Scholar
  60. Kokare DM, Kyzar EJ, Zhang H, Sakharkar AJ, Pandey SC (2017) Adolescent alcohol exposure-induced changes in alpha-melanocyte stimulating hormone and neuropeptide Y pathways via histone acetylation in the brain during adulthood. Int J Neuropsychopharmacol 20(9):758–768.  https://doi.org/10.1093/ijnp/pyx041CrossRefPubMedPubMedCentralGoogle Scholar
  61. Kumar D, Deb I, Chakraborty J, Mukhopadhyay S, Das S (2011) A polymorphism of the CREB binding protein (CREBBP) gene is a risk factor for addiction. Brain Res 1406:59–64.  https://doi.org/10.1016/j.brainres.2011.05.048CrossRefPubMedGoogle Scholar
  62. Li CC, Dai RM, Chen E, Longo DL (1994) Phosphorylation of NF-KB1-p50 is involved in NF-kappa B activation and stable DNA binding. J Biol Chem 269(48):30089–30092PubMedGoogle Scholar
  63. Liu C, Marioni RE, Hedman AK, Pfeiffer L, Tsai PC, Reynolds LM, Just AC, Duan Q, Boer CG, Tanaka T, Elks CE, Aslibekyan S, Brody JA, Kuhnel B, Herder C, Almli LM, Zhi D, Wang Y, Huan T, Yao C, Mendelson MM, Joehanes R, Liang L, Love SA, Guan W, Shah S, McRae AF, Kretschmer A, Prokisch H, Strauch K, Peters A, Visscher PM, Wray NR, Guo X, Wiggins KL, Smith AK, Binder EB, Ressler KJ, Irvin MR, Absher DM, Hernandez D, Ferrucci L, Bandinelli S, Lohman K, Ding J, Trevisi L, Gustafsson S, Sandling JH, Stolk L, Uitterlinden AG, Yet I, Castillo-Fernandez JE, Spector TD, Schwartz JD, Vokonas P, Lind L, Li Y, Fornage M, Arnett DK, Wareham NJ, Sotoodehnia N, Ong KK, van Meurs JB, Conneely KN, Baccarelli AA, Deary IJ, Bell JT, North KE, Liu Y, Waldenberger M, London SJ, Ingelsson E, Levy D (2016) A DNA methylation biomarker of alcohol consumption. Mol Psychiatry.  https://doi.org/10.1038/mp.2016.192
  64. Liu X, Hao PD, Yang MF, Sun JY, Mao LL, Fan CD, Zhang ZY, Li DW, Yang XY, Sun BL, Zhang HT (2017) The phosphodiesterase-4 inhibitor roflumilast decreases ethanol consumption in C57BL/6J mice. Psychopharmacology (Berl) 234(16):2409–2419.  https://doi.org/10.1007/s00213-017-4631-8CrossRefGoogle Scholar
  65. Lobo MK, Covington HE 3rd, Chaudhury D, Friedman AK, Sun H, Damez-Werno D, Dietz DM, Zaman S, Koo JW, Kennedy PJ, Mouzon E, Mogri M, Neve RL, Deisseroth K, Han MH, Nestler EJ (2010) Cell type-specific loss of BDNF signaling mimics optogenetic control of cocaine reward. Science 330(6002):385–390.  https://doi.org/10.1126/science.1188472ADSCrossRefPubMedPubMedCentralGoogle Scholar
  66. Logrip ML (2015) Phosphodiesterase regulation of alcohol drinking in rodents. Alcohol 49(8):795–802.  https://doi.org/10.1016/j.alcohol.2015.03.007CrossRefPubMedPubMedCentralGoogle Scholar
  67. Logrip ML, Vendruscolo LF, Schlosburg JE, Koob GF, Zorrilla EP (2014) Phosphodiesterase 10A regulates alcohol and saccharin self-administration in rats. Neuropsychopharmacology 39(7):1722–1731.  https://doi.org/10.1038/npp.2014.20CrossRefPubMedPubMedCentralGoogle Scholar
  68. Logrip ML, Barak S, Warnault V, Ron D (2015) Corticostriatal BDNF and alcohol addiction. Brain Res 1628(Pt A):60–67.  https://doi.org/10.1016/j.brainres.2015.03.025CrossRefPubMedPubMedCentralGoogle Scholar
  69. Masood U, Sharma A, Nijjar S, Krenzer B (2016) Unusual case of an alcoholic with liver injury from sulfasalazine use. J Basic Clin Pharm 8(1):38–39.  https://doi.org/10.4103/0976-0105.195126CrossRefPubMedPubMedCentralGoogle Scholar
  70. Mayr B, Montminy M (2001) Transcriptional regulation by the phosphorylation-dependent factor CREB. Nat Rev Mol Cell Biol 2(8):599–609.  https://doi.org/10.1038/35085068CrossRefPubMedGoogle Scholar
  71. Meffert MK, Chang JM, Wiltgen BJ, Fanselow MS, Baltimore D (2003) NF-kappa B functions in synaptic signaling and behavior. Nat Neurosci 6(10):1072–1078.  https://doi.org/10.1038/nn1110CrossRefPubMedGoogle Scholar
  72. Meier FM, Frerix M, Hermann W, Muller-Ladner U (2013) Current immunotherapy in rheumatoid arthritis. Immunotherapy 5(9):955–974.  https://doi.org/10.2217/imt.13.94CrossRefPubMedGoogle Scholar
  73. 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(2):238–250.  https://doi.org/10.1111/j.1369-1600.2010.00275.xCrossRefPubMedGoogle Scholar
  74. Moonat S, Sakharkar AJ, Zhang H, Tang L, Pandey SC (2013) Aberrant histone deacetylase2-mediated histone modifications and synaptic plasticity in the amygdala predisposes to anxiety and alcoholism. Biol Psychiatry 73(8):763–773.  https://doi.org/10.1016/j.biopsych.2013.01.012CrossRefPubMedPubMedCentralGoogle Scholar
  75. Moreno S, Farioli-Vecchioli S, Ceru MP (2004) Immunolocalization of peroxisome proliferator-activated receptors and retinoid X receptors in the adult rat CNS. Neuroscience 123(1):131–145CrossRefPubMedGoogle Scholar
  76. Nair A, Bonneau RH (2006) Stress-induced elevation of glucocorticoids increases microglia proliferation through NMDA receptor activation. J Neuroimmunol 171(1–2):72–85.  https://doi.org/10.1016/j.jneuroim.2005.09.012CrossRefPubMedGoogle Scholar
  77. Nash JF Jr, Maickel RP (1985) Stress-induced consumption of ethanol by rats. Life Sci 37(8):757–765CrossRefPubMedGoogle Scholar
  78. Nash JF Jr, Maickel RP (1988) The role of the hypothalamic-pituitary-adrenocortical axis in post-stress induced ethanol consumption by rats. Prog Neuropsychopharmacol Biol Psychiatry 12(5):653–671CrossRefPubMedGoogle Scholar
  79. Nedic G, Perkovic MN, Sviglin KN, Muck-Seler D, Borovecki F, Pivac N (2013) Brain-derived neurotrophic factor Val66Met polymorphism and alcohol-related phenotypes. Prog Neuropsychopharmacol Biol Psychiatry 40:193–198.  https://doi.org/10.1016/j.pnpbp.2012.09.005CrossRefPubMedGoogle Scholar
  80. Okvist A, Johansson S, Kuzmin A, Bazov I, Merino-Martinez R, Ponomarev I, Mayfield RD, Harris RA, Sheedy D, Garrick T, Harper C, Hurd YL, Terenius L, Ekstrom TJ, Bakalkin G, Yakovleva T (2007) Neuroadaptations in human chronic alcoholics: dysregulation of the NF-kappaB system. PLoS One 2(9):e930.  https://doi.org/10.1371/journal.pone.0000930ADSCrossRefPubMedPubMedCentralGoogle Scholar
  81. Olsen CM, Liu QS (2016) Phosphodiesterase 4 inhibitors and drugs of abuse: current knowledge and therapeutic opportunities. Front Biol (Beijing) 11(5):376–386.  https://doi.org/10.1007/s11515-016-1424-0CrossRefGoogle Scholar
  82. Page CP, Spina D (2011) Phosphodiesterase inhibitors in the treatment of inflammatory diseases. Handb Exp Pharmacol 204:391–414.  https://doi.org/10.1007/978-3-642-17969-3_17CrossRefGoogle Scholar
  83. Pal A, Chakraborty J, Das S (2014) Association of CREB1 gene polymorphism with drug seeking behaviour in eastern Indian addicts. Neurosci Lett 570:53–57.  https://doi.org/10.1016/j.neulet.2014.03.064CrossRefPubMedGoogle Scholar
  84. Pandey SC, Mittal N, Lumeng L, Li TK (1999) Involvement of the cyclic AMP-responsive element binding protein gene transcription factor in genetic preference for alcohol drinking behavior. Alcohol Clin Exp Res 23(9):1425–1434CrossRefPubMedGoogle Scholar
  85. Pandey SC, Roy A, Mittal N (2001) Effects of chronic ethanol intake and its withdrawal on the expression and phosphorylation of the CREB gene transcription factor in rat cortex. J Pharmacol Exp Ther 296(3):857–868PubMedGoogle Scholar
  86. Pandey SC, Roy A, Zhang H (2003) The decreased phosphorylation of cyclic adenosine monophosphate (cAMP) response element binding (CREB) protein in the central amygdala acts as a molecular substrate for anxiety related to ethanol withdrawal in rats. Alcohol Clin Exp Res 27(3):396–409.  https://doi.org/10.1097/01.ALC.0000056616.81971.49CrossRefPubMedGoogle Scholar
  87. Pandey SC, Roy A, Zhang H, Xu T (2004) Partial deletion of the cAMP response element-binding protein gene promotes alcohol-drinking behaviors. J Neurosci 24(21):5022–5030.  https://doi.org/10.1523/JNEUROSCI.5557-03.2004CrossRefPubMedGoogle Scholar
  88. Pandey SC, Zhang H, Roy A, Xu T (2005) Deficits in amygdaloid cAMP-responsive element-binding protein signaling play a role in genetic predisposition to anxiety and alcoholism. J Clin Invest 115(10):2762–2773.  https://doi.org/10.1172/JCI24381CrossRefPubMedPubMedCentralGoogle Scholar
  89. Pandey SC, Ugale R, Zhang H, Tang L, Prakash A (2008) Brain chromatin remodeling: a novel mechanism of alcoholism. J Neurosci 28(14):3729–3737.  https://doi.org/10.1523/JNEUROSCI.5731-07.2008CrossRefPubMedGoogle Scholar
  90. Pandey SC, Sakharkar AJ, Tang L, Zhang H (2015) Potential role of adolescent alcohol exposure-induced amygdaloid histone modifications in anxiety and alcohol intake during adulthood. Neurobiol Dis 82:607–619.  https://doi.org/10.1016/j.nbd.2015.03.019CrossRefPubMedPubMedCentralGoogle Scholar
  91. Pascual G, Fong AL, Ogawa S, Gamliel A, Li AC, Perissi V, Rose DW, Willson TM, Rosenfeld MG, Glass CK (2005) A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature 437(7059):759–763.  https://doi.org/10.1038/nature03988ADSCrossRefPubMedPubMedCentralGoogle Scholar
  92. Pascual M, Boix J, Felipo V, Guerri C (2009) Repeated alcohol administration during adolescence causes changes in the mesolimbic dopaminergic and glutamatergic systems and promotes alcohol intake in the adult rat. J Neurochem 108(4):920–931.  https://doi.org/10.1111/j.1471-4159.2008.05835.xCrossRefPubMedGoogle Scholar
  93. Pascual M, Do Couto BR, Alfonso-Loeches S, Aguilar MA, Rodriguez-Arias M, Guerri C (2012) Changes in histone acetylation in the prefrontal cortex of ethanol-exposed adolescent rats are associated with ethanol-induced place conditioning. Neuropharmacology 62(7):2309–2319.  https://doi.org/10.1016/j.neuropharm.2012.01.011CrossRefPubMedGoogle Scholar
  94. Pathak H, Frieling H, Bleich S, Glahn A, Heberlein A, Haschemi Nassab M, Hillemacher T, Burkert A, Rhein M (2017) Promoter polymorphism rs886205 genotype interacts with DNA methylation of the ALDH2 regulatory region in alcohol dependence. Alcohol Alcohol 52(3):269–276.  https://doi.org/10.1093/alcalc/agw106PubMedGoogle Scholar
  95. Pena CJ, Bagot RC, Labonte B, Nestler EJ (2014) Epigenetic signaling in psychiatric disorders. J Mol Biol 426(20):3389–3412.  https://doi.org/10.1016/j.jmb.2014.03.016CrossRefPubMedPubMedCentralGoogle Scholar
  96. Perkins ND (1997) Achieving transcriptional specificity with NF-kappa B. Int J Biochem Cell Biol 29(12):1433–1448CrossRefPubMedGoogle Scholar
  97. Philibert RA, Gunter TD, Beach SR, Brody GH, Madan A (2008a) MAOA methylation is associated with nicotine and alcohol dependence in women. Am J Med Genet B Neuropsychiatr Genet 147B(5):565–570.  https://doi.org/10.1002/ajmg.b.30778CrossRefPubMedGoogle Scholar
  98. Philibert RA, Sandhu H, Hollenbeck N, Gunter T, Adams W, Madan A (2008b) The relationship of 5HTT (SLC6A4) methylation and genotype on mRNA expression and liability to major depression and alcohol dependence in subjects from the Iowa Adoption Studies. Am J Med Genet B Neuropsychiatr Genet 147B(5):543–549.  https://doi.org/10.1002/ajmg.b.30657CrossRefPubMedGoogle Scholar
  99. Philibert RA, Plume JM, Gibbons FX, Brody GH, Beach SR (2012) The impact of recent alcohol use on genome wide DNA methylation signatures. Front Genet 3:54.  https://doi.org/10.3389/fgene.2012.00054CrossRefPubMedPubMedCentralGoogle Scholar
  100. Philibert RA, Penaluna B, White T, Shires S, Gunter T, Liesveld J, Erwin C, Hollenbeck N, Osborn T (2014) A pilot examination of the genome-wide DNA methylation signatures of subjects entering and exiting short-term alcohol dependence treatment programs. Epigenetics 9(9):1212–1219.  https://doi.org/10.4161/epi.32252CrossRefPubMedPubMedCentralGoogle Scholar
  101. Pivac N, Kim B, Nedic G, Joo YH, Kozaric-Kovacic D, Hong JP, Muck-Seler D (2009) Ethnic differences in brain-derived neurotrophic factor Val66Met polymorphism in Croatian and Korean healthy participants. Croat Med J 50(1):43–48CrossRefPubMedPubMedCentralGoogle Scholar
  102. Ponomarev I, Wang S, Zhang L, Harris RA, Mayfield RD (2012) Gene coexpression networks in human brain identify epigenetic modifications in alcohol dependence. J Neurosci 32(5):1884–1897.  https://doi.org/10.1523/JNEUROSCI.3136-11.2012CrossRefPubMedPubMedCentralGoogle Scholar
  103. Ponomarev I, Stelly CE, Morikawa H, Blednov YA, Mayfield RD, Harris RA (2017) Mechanistic insights into epigenetic modulation of ethanol consumption. Alcohol 60:95–101.  https://doi.org/10.1016/j.alcohol.2017.01.016CrossRefPubMedGoogle Scholar
  104. Qiang M, Denny A, Lieu M, Carreon S, Li J (2011) Histone H3K9 modifications are a local chromatin event involved in ethanol-induced neuroadaptation of the NR2B gene. Epigenetics 6(9):1095–1104.  https://doi.org/10.4161/epi.6.9.16924CrossRefPubMedPubMedCentralGoogle Scholar
  105. Qiang M, Li JG, Denny AD, Yao JM, Lieu M, Zhang K, Carreon S (2014) Epigenetic mechanisms are involved in the regulation of ethanol consumption in mice. Int J Neuropsychopharmacol 18(2).  https://doi.org/10.1093/ijnp/pyu072
  106. Qiao X, Yin F, Ji Y, Li Y, Yan P, Lai J (2017) 5-Aza-2′-deoxycytidine in the medial prefrontal cortex regulates alcohol-related behavior and Ntf3-TrkC expression in rats. PLoS One 12(6):e0179469.  https://doi.org/10.1371/journal.pone.0179469CrossRefPubMedPubMedCentralGoogle Scholar
  107. Ratman D, Vanden Berghe W, Dejager L, Libert C, Tavernier J, Beck IM, De Bosscher K (2013) How glucocorticoid receptors modulate the activity of other transcription factors: a scope beyond tethering. Mol Cell Endocrinol 380(1–2):41–54.  https://doi.org/10.1016/j.mce.2012.12.014CrossRefPubMedGoogle Scholar
  108. Ray LA, Bujarski S, Shoptaw S, Roche DJ, Heinzerling K, Miotto K (2017) Development of the neuroimmune modulator ibudilast for the treatment of alcoholism: a randomized, placebo-controlled, human laboratory trial. Neuropsychopharmacology 42(9):1776–1788.  https://doi.org/10.1038/npp.2017.10CrossRefPubMedGoogle Scholar
  109. Reddy TE, Pauli F, Sprouse RO, Neff NF, Newberry KM, Garabedian MJ, Myers RM (2009) Genomic determination of the glucocorticoid response reveals unexpected mechanisms of gene regulation. Genome Res 19(12):2163–2171.  https://doi.org/10.1101/gr.097022.109CrossRefPubMedPubMedCentralGoogle Scholar
  110. Repunte-Canonigo V, Lutjens R, van der Stap LD, Sanna PP (2007) Increased expression of protein kinase A inhibitor alpha (PKI-alpha) and decreased PKA-regulated genes in chronic intermittent alcohol exposure. Brain Res 1138:48–56.  https://doi.org/10.1016/j.brainres.2006.09.115CrossRefPubMedPubMedCentralGoogle Scholar
  111. Robinson SL, Thiele TE (2017) The role of neuropeptide Y (NPY) in alcohol and drug abuse disorders. Int Rev Neurobiol 136:177–197.  https://doi.org/10.1016/bs.irn.2017.06.005CrossRefPubMedGoogle Scholar
  112. Rosenson RS, Wright RS, Farkouh M, Plutzky J (2012) Modulating peroxisome proliferator-activated receptors for therapeutic benefit? Biology, clinical experience, and future prospects. Am Heart J 164(5):672–680.  https://doi.org/10.1016/j.ahj.2012.06.023CrossRefPubMedPubMedCentralGoogle Scholar
  113. Rulten SL, Ripley TL, Hunt CL, Stephens DN, Mayne LV (2006) Sp1 and NFkappaB pathways are regulated in brain in response to acute and chronic ethanol. Genes Brain Behav 5(3):257–273.  https://doi.org/10.1111/j.1601-183X.2005.00157.xCrossRefPubMedGoogle Scholar
  114. Rupprecht R, Reul JM, van Steensel B, Spengler D, Soder M, Berning B, Holsboer F, Damm K (1993) Pharmacological and functional characterization of human mineralocorticoid and glucocorticoid receptor ligands. Eur J Pharmacol 247(2):145–154CrossRefPubMedGoogle Scholar
  115. Russell MA, Almeida DM, Maggs JL (2017) Stressor-related drinking and future alcohol problems among university students. Psychol Addict Behav 31(6):676–687.  https://doi.org/10.1037/adb0000303CrossRefPubMedGoogle Scholar
  116. Sacconnay L, Carrupt PA, Nurisso A (2016) Human sirtuins: structures and flexibility. J Struct Biol 196(3):534–542.  https://doi.org/10.1016/j.jsb.2016.10.008CrossRefPubMedGoogle Scholar
  117. Sakharkar AJ, Zhang H, Tang L, Shi G, Pandey SC (2012) Histone deacetylases (HDAC)-induced histone modifications in the amygdala: a role in rapid tolerance to the anxiolytic effects of ethanol. Alcohol Clin Exp Res 36(1):61–71.  https://doi.org/10.1111/j.1530-0277.2011.01581.xCrossRefPubMedGoogle Scholar
  118. Sakharkar AJ, Zhang H, Tang L, Baxstrom K, Shi G, Moonat S, Pandey SC (2014) Effects of histone deacetylase inhibitors on amygdaloid histone acetylation and neuropeptide Y expression: a role in anxiety-like and alcohol-drinking behaviours. Int J Neuropsychopharmacol 17(8):1207–1220.  https://doi.org/10.1017/S1461145714000054CrossRefPubMedPubMedCentralGoogle Scholar
  119. Sakharkar AJ, Vetreno RP, Zhang H, Kokare DM, Crews FT, Pandey SC (2016) A role for histone acetylation mechanisms in adolescent alcohol exposure-induced deficits in hippocampal brain-derived neurotrophic factor expression and neurogenesis markers in adulthood. Brain Struct Funct 221(9):4691–4703.  https://doi.org/10.1007/s00429-016-1196-yCrossRefPubMedPubMedCentralGoogle Scholar
  120. Schellekens AF, de Jong CA, Buitelaar JK, Verkes RJ (2015) Co-morbid anxiety disorders predict early relapse after inpatient alcohol treatment. Eur Psychiatry 30(1):128–136.  https://doi.org/10.1016/j.eurpsy.2013.08.006CrossRefPubMedGoogle Scholar
  121. Shah P, Mudaliar S (2010) Pioglitazone: side effect and safety profile. Expert Opin Drug Saf 9(2):347–354.  https://doi.org/10.1517/14740331003623218CrossRefPubMedGoogle Scholar
  122. Shakibaei M, John T, Schulze-Tanzil G, Lehmann I, Mobasheri A (2007) Suppression of NF-kappaB activation by curcumin leads to inhibition of expression of cyclo-oxygenase-2 and matrix metalloproteinase-9 in human articular chondrocytes: implications for the treatment of osteoarthritis. Biochem Pharmacol 73(9):1434–1445.  https://doi.org/10.1016/j.bcp.2007.01.005CrossRefPubMedGoogle Scholar
  123. Sharrett-Field L, Butler TR, Berry JN, Reynolds AR, Prendergast MA (2013) Mifepristone pretreatment reduces ethanol withdrawal severity in vivo. Alcohol Clin Exp Res 37(8):1417–1423.  https://doi.org/10.1111/acer.12093CrossRefPubMedPubMedCentralGoogle Scholar
  124. Shibasaki M, Mizuno K, Kurokawa K, Ohkuma S (2011) Enhancement of histone acetylation in midbrain of mice with ethanol physical dependence and its withdrawal. Synapse 65(11):1244–1250.  https://doi.org/10.1002/syn.20947CrossRefPubMedGoogle Scholar
  125. Shimizu E, Hashimoto K, Iyo M (2004) Ethnic difference of the BDNF 196G/A (val66met) polymorphism frequencies: the possibility to explain ethnic mental traits. Am J Med Genet B Neuropsychiatr Genet 126B(1):122–123.  https://doi.org/10.1002/ajmg.b.20118CrossRefPubMedGoogle Scholar
  126. Silva AJ, Kogan JH, Frankland PW, Kida S (1998) CREB and memory. Annu Rev Neurosci 21:127–148.  https://doi.org/10.1146/annurev.neuro.21.1.127CrossRefPubMedGoogle Scholar
  127. Simon-O’Brien E, Alaux-Cantin S, Warnault V, Buttolo R, Naassila M, Vilpoux C (2015) The histone deacetylase inhibitor sodium butyrate decreases excessive ethanol intake in dependent animals. Addict Biol 20(4):676–689.  https://doi.org/10.1111/adb.12161CrossRefPubMedGoogle Scholar
  128. Singh S, Aggarwal BB (1995) Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]. J Biol Chem 270(42):24995–25000CrossRefPubMedGoogle Scholar
  129. Soderling TR (1999) The Ca-calmodulin-dependent protein kinase cascade. Trends Biochem Sci 24(6):232–236CrossRefPubMedGoogle Scholar
  130. Somkuwar SS, Vendruscolo LF, Fannon MJ, Schmeichel BE, Nguyen TB, Guevara J, Sidhu H, Contet C, Zorrilla EP, Mandyam CD (2017) Abstinence from prolonged ethanol exposure affects plasma corticosterone, glucocorticoid receptor signaling and stress-related behaviors. Psychoneuroendocrinology 84:17–31.  https://doi.org/10.1016/j.psyneuen.2017.06.006CrossRefPubMedGoogle Scholar
  131. Spanagel R, Noori HR, Heilig M (2014) Stress and alcohol interactions: animal studies and clinical significance. Trends Neurosci 37(4):219–227.  https://doi.org/10.1016/j.tins.2014.02.006CrossRefPubMedGoogle Scholar
  132. Stopponi S, Somaini L, Cippitelli A, Cannella N, Braconi S, Kallupi M, Ruggeri B, Heilig M, Demopulos G, Gaitanaris G, Massi M, Ciccocioppo R (2011) Activation of nuclear PPARgamma receptors by the antidiabetic agent pioglitazone suppresses alcohol drinking and relapse to alcohol seeking. Biol Psychiatry 69(7):642–649.  https://doi.org/10.1016/j.biopsych.2010.12.010CrossRefPubMedGoogle Scholar
  133. Stopponi S, de Guglielmo G, Somaini L, Cippitelli A, Cannella N, Kallupi M, Ubaldi M, Heilig M, Demopulos G, Gaitanaris G, Ciccocioppo R (2013) Activation of PPARgamma by pioglitazone potentiates the effects of naltrexone on alcohol drinking and relapse in msP rats. Alcohol Clin Exp Res 37(8):1351–1360.  https://doi.org/10.1111/acer.12091CrossRefPubMedGoogle Scholar
  134. Subramanian S, Bates SE, Wright JJ, Espinoza-Delgado I, Piekarz RL (2010) Clinical toxicities of histone deacetylase inhibitors. Pharmaceuticals (Basel) 3(9):2751–2767.  https://doi.org/10.3390/ph3092751CrossRefGoogle Scholar
  135. Tajuddin N, Moon KH, Marshall SA, Nixon K, Neafsey EJ, Kim HY, Collins MA (2014) Neuroinflammation and neurodegeneration in adult rat brain from binge ethanol exposure: abrogation by docosahexaenoic acid. PLoS One 9(7):e101223.  https://doi.org/10.1371/journal.pone.0101223ADSCrossRefPubMedPubMedCentralGoogle Scholar
  136. Takeuchi Y, Fukunaga K (2003) Differential regulation of NF-kappaB, SRE and CRE by dopamine D1 and D2 receptors in transfected NG108-15 cells. J Neurochem 85(3):729–739CrossRefPubMedGoogle Scholar
  137. Tanigawara Y, Kita T, Aoyama N, Gobara M, Komada F, Sakai T, Kasuga M, Hatanaka H, Sakaeda T, Okumura K (2002) N-acetyltransferase 2 genotype-related sulfapyridine acetylation and its adverse events. Biol Pharm Bull 25(8):1058–1062CrossRefPubMedGoogle Scholar
  138. Tao X, Finkbeiner S, Arnold DB, Shaywitz AJ, Greenberg ME (1998) Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron 20(4):709–726CrossRefPubMedGoogle Scholar
  139. ter Heegde F, De Rijk RH, Vinkers CH (2015) The brain mineralocorticoid receptor and stress resilience. Psychoneuroendocrinology 52:92–110.  https://doi.org/10.1016/j.psyneuen.2014.10.022CrossRefPubMedGoogle Scholar
  140. Titus DJ, Oliva AA, Wilson NM, Atkins CM (2015) Phosphodiesterase inhibitors as therapeutics for traumatic brain injury. Curr Pharm Des 21(3):332–342CrossRefPubMedGoogle Scholar
  141. Tiwari V, Chopra K (2013a) Protective effect of curcumin against chronic alcohol-induced cognitive deficits and neuroinflammation in the adult rat brain. Neuroscience 244:147–158.  https://doi.org/10.1016/j.neuroscience.2013.03.042CrossRefPubMedGoogle Scholar
  142. Tiwari V, Chopra K (2013b) Resveratrol abrogates alcohol-induced cognitive deficits by attenuating oxidative-nitrosative stress and inflammatory cascade in the adult rat brain. Neurochem Int 62(6):861–869.  https://doi.org/10.1016/j.neuint.2013.02.012CrossRefPubMedGoogle Scholar
  143. Truitt JM, Blednov YA, Benavidez JM, Black M, Ponomareva O, Law J, Merriman M, Horani S, Jameson K, Lasek AW, Harris RA, Mayfield RD (2016) Inhibition of IKKbeta reduces ethanol consumption in C57BL/6J mice. eNeuro 3(5).  https://doi.org/10.1523/ENEURO.0256-16.2016
  144. Tulisiak CT, Harris RA, Ponomarev I (2017) DNA modifications in models of alcohol use disorders. Alcohol 60:19–30.  https://doi.org/10.1016/j.alcohol.2016.11.004CrossRefPubMedGoogle Scholar
  145. Uhart M, Oswald L, McCaul ME, Chong R, Wand GS (2006) Hormonal responses to psychological stress and family history of alcoholism. Neuropsychopharmacology 31(10):2255–2263.  https://doi.org/10.1038/sj.npp.1301063PubMedGoogle Scholar
  146. Vendruscolo LF, Barbier E, Schlosburg JE, Misra KK, Whitfield TW Jr, Logrip ML, Rivier C, Repunte-Canonigo V, Zorrilla EP, Sanna PP, Heilig M, Koob GF (2012) Corticosteroid-dependent plasticity mediates compulsive alcohol drinking in rats. J Neurosci 32(22):7563–7571.  https://doi.org/10.1523/JNEUROSCI.0069-12.2012CrossRefPubMedPubMedCentralGoogle Scholar
  147. Vendruscolo LF, Estey D, Goodell V, Macshane LG, Logrip ML, Schlosburg JE, McGinn MA, Zamora-Martinez ER, Belanoff JK, Hunt HJ, Sanna PP, George O, Koob GF, Edwards S, Mason BJ (2015) Glucocorticoid receptor antagonism decreases alcohol seeking in alcohol-dependent individuals. J Clin Invest 125(8):3193–3197.  https://doi.org/10.1172/JCI79828CrossRefPubMedPubMedCentralGoogle Scholar
  148. Wand GS, Dobs AS (1991) Alterations in the hypothalamic-pituitary-adrenal axis in actively drinking alcoholics. J Clin Endocrinol Metab 72(6):1290–1295.  https://doi.org/10.1210/jcem-72-6-1290CrossRefPubMedGoogle Scholar
  149. Wang F, Xu H, Zhao H, Gelernter J, Zhang H (2016) DNA co-methylation modules in postmortem prefrontal cortex tissues of European Australians with alcohol use disorders. Sci Rep 6:19430.  https://doi.org/10.1038/srep19430ADSCrossRefPubMedPubMedCentralGoogle Scholar
  150. Warden A, Truitt J, Merriman M, Ponomareva O, Jameson K, Ferguson LB, Mayfield RD, Harris RA (2016) Localization of PPAR isotypes in the adult mouse and human brain. Sci Rep 6:27618.  https://doi.org/10.1038/srep27618ADSCrossRefPubMedPubMedCentralGoogle Scholar
  151. 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.  https://doi.org/10.1038/tp.2013.4CrossRefPubMedPubMedCentralGoogle Scholar
  152. Wen RT, Zhang M, Qin WJ, Liu Q, Wang WP, Lawrence AJ, Zhang HT, Liang JH (2012) The phosphodiesterase-4 (PDE4) inhibitor rolipram decreases ethanol seeking and consumption in alcohol-preferring Fawn-Hooded rats. Alcohol Clin Exp Res 36(12):2157–2167.  https://doi.org/10.1111/j.1530-0277.2012.01845.xCrossRefPubMedPubMedCentralGoogle Scholar
  153. Witkiewitz K (2011) Predictors of heavy drinking during and following treatment. Psychol Addict Behav 25(3):426–438.  https://doi.org/10.1037/a0022889CrossRefPubMedPubMedCentralGoogle Scholar
  154. Wojnar M, Brower KJ, Strobbe S, Ilgen M, Matsumoto H, Nowosad I, Sliwerska E, Burmeister M (2009) Association between Val66Met brain-derived neurotrophic factor (BDNF) gene polymorphism and post-treatment relapse in alcohol dependence. Alcohol Clin Exp Res 33(4):693–702.  https://doi.org/10.1111/j.1530-0277.2008.00886.xCrossRefPubMedPubMedCentralGoogle Scholar
  155. Wolstenholme JT, Warner JA, Capparuccini MI, Archer KJ, Shelton KL, Miles MF (2011) Genomic analysis of individual differences in ethanol drinking: evidence for non-genetic factors in C57BL/6 mice. PLoS One 6(6):e21100.  https://doi.org/10.1371/journal.pone.0021100ADSCrossRefPubMedPubMedCentralGoogle Scholar
  156. Yakovleva T, Bazov I, Watanabe H, Hauser KF, Bakalkin G (2011) Transcriptional control of maladaptive and protective responses in alcoholics: a role of the NF-kappaB system. Brain Behav Immun 25(Suppl 1):S29–S38.  https://doi.org/10.1016/j.bbi.2010.12.019CrossRefPubMedGoogle Scholar
  157. Yang X, Horn K, Baraban JM, Wand GS (1998) Chronic ethanol administration decreases phosphorylation of cyclic AMP response element-binding protein in granule cells of rat cerebellum. J Neurochem 70(1):224–232CrossRefPubMedGoogle Scholar
  158. Yang X, Oswald L, Wand G (2003) The cyclic AMP/protein kinase A signal transduction pathway modulates tolerance to sedative and hypothermic effects of ethanol. Alcohol Clin Exp Res 27(8):1220–1225.  https://doi.org/10.1097/01.ALC.0000081626.02910.19CrossRefPubMedGoogle Scholar
  159. You C, Zhang H, Sakharkar AJ, Teppen T, Pandey SC (2014) Reversal of deficits in dendritic spines, BDNF and Arc expression in the amygdala during alcohol dependence by HDAC inhibitor treatment. Int J Neuropsychopharmacol 17(2):313–322.  https://doi.org/10.1017/S1461145713001144CrossRefPubMedGoogle Scholar
  160. Zhang R, Miao Q, Wang C, Zhao R, Li W, Haile CN, Hao W, Zhang XY (2013) Genome-wide DNA methylation analysis in alcohol dependence. Addict Biol 18(2):392–403.  https://doi.org/10.1111/adb.12037CrossRefPubMedGoogle Scholar
  161. Zhao R, Zhang R, Li W, Liao Y, Tang J, Miao Q, Hao W (2013) Genome-wide DNA methylation patterns in discordant sib pairs with alcohol dependence. Asia Pac Psychiatry 5(1):39–50.  https://doi.org/10.1111/appy.12010CrossRefPubMedGoogle Scholar
  162. Zhu Y, Qi C, Calandra C, Rao MS, Reddy JK (1996) Cloning and identification of mouse steroid receptor coactivator-1 (mSRC-1), as a coactivator of peroxisome proliferator-activated receptor gamma. Gene Expr 6(3):185–195PubMedGoogle Scholar
  163. Zhu ZZ, Hou L, Bollati V, Tarantini L, Marinelli B, Cantone L, Yang AS, Vokonas P, Lissowska J, Fustinoni S, Pesatori AC, Bonzini M, Apostoli P, Costa G, Bertazzi PA, Chow WH, Schwartz J, Baccarelli A (2012) Predictors of global methylation levels in blood DNA of healthy subjects: a combined analysis. Int J Epidemiol 41(1):126–139.  https://doi.org/10.1093/ije/dyq154CrossRefPubMedGoogle Scholar
  164. Zou J, Crews F (2010) Induction of innate immune gene expression cascades in brain slice cultures by ethanol: key role of NF-kappaB and proinflammatory cytokines. Alcohol Clin Exp Res 34(5):777–789.  https://doi.org/10.1111/j.1530-0277.2010.01150.xCrossRefPubMedGoogle Scholar
  165. Zovkic IB, Guzman-Karlsson MC, Sweatt JD (2013) Epigenetic regulation of memory formation and maintenance. Learn Mem 20(2):61–74.  https://doi.org/10.1101/lm.026575.112CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of PsychiatryUniversity of Illinois at ChicagoChicagoUSA
  2. 2.Department of Behavioral NeuroscienceOregon Health and Science UniversityPortlandUSA

Personalised recommendations