Cellular and Molecular Life Sciences

, Volume 67, Issue 1, pp 73–88 | Cite as

Neuroscience of alcoholism: molecular and cellular mechanisms

  • Sachin Moonat
  • Bela G. Starkman
  • Amul Sakharkar
  • Subhash C. PandeyEmail author


Alcohol use and abuse appear to be related to neuroadaptive changes at functional, neurochemical, and structural levels. Acute and chronic ethanol exposure have been shown to modulate function of the activity-dependent gene transcription factor, cAMP-responsive element binding (CREB) protein in the brain, which may be associated with the development of alcoholism. Study of the downstream effectors of CREB have identified several important CREB-related genes, such as neuropeptide Y, brain-derived neurotrophic factor, activity-regulated cytoskeleton-associated protein, and corticotrophin-releasing factor, that may play a crucial role in the behavioral effects of ethanol and molecular changes in the specific neurocircuitry that underlie both alcohol addiction and a genetic predisposition to alcoholism. Brain chromatin remodeling due to histone covalent modifications may also be involved in mediating the behavioral effects and neuroadaptive changes that occur during ethanol exposure. This review outlines progressive neuroscience research into molecular and epigenetic mechanisms of alcoholism.


Alcoholism Epigenetic CREB BDNF NPY CRF Arc Anxiety Brain 



The studies conducted in the laboratory of Dr. S.C. Pandey were supported by the grants from the National Institute on Alcohol Abuse and Alcoholism (AA-010005; AA-013341; AA-016690; AA-015626) and the Department of Veterans Affairs (Merit Review Grant; Research Career Scientist award).


  1. 1.
    Koob GF (2003) Alcoholism: allostasis and beyond. Alcohol Clin Exp Res 27:232–243PubMedGoogle Scholar
  2. 2.
    Andreasen NC, Black DW (2006) Introductory textbook of psychiatry. American Psychiatric Publication, WashingtonGoogle Scholar
  3. 3.
    Nestler EJ (2001) Molecular basis of long-term plasticity underlying addiction. Nat Rev Neurosci 2:119–128PubMedGoogle Scholar
  4. 4.
    Koob GF, Sanna PP, Bloom FE (1998) Neuroscience of addiction. Neuron 21:467–476PubMedGoogle Scholar
  5. 5.
    Pandey SC (2004) The gene transcription factor cyclic AMP-responsive element binding protein: role in positive and negative affective states of alcohol addiction. Pharmacol Ther 104:47–58PubMedGoogle Scholar
  6. 6.
    Gonzales RA, Job MO, Doyon WM (2004) The role of mesolimbic dopamine in the development and maintenance of ethanol reinforcement. Pharmacol Ther 103:121–146PubMedGoogle Scholar
  7. 7.
    Conway KP, Compton W, Stinson FS, Grant BF (2006) Lifetime comorbidity of DSM-IV mood and anxiety disorders and specific drug use disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry 67:247–257PubMedGoogle Scholar
  8. 8.
    Schuckit MA, Hesselbrock V (1994) Alcohol dependence and anxiety disorders: what is the relationship? Am J Psychiatry 151:1723–1734PubMedGoogle Scholar
  9. 9.
    Carlezon WA Jr, Duman RS, Nestler EJ (2005) The many faces of CREB. Trends Neurosci 28:436–445PubMedGoogle Scholar
  10. 10.
    Spanagel R (2009) Alcoholism: a systems approach from molecular physiology to addictive behavior. Physiol Rev 89:649–705PubMedGoogle Scholar
  11. 11.
    Morrow AL, Ferrani-Kile K, Davis MI, Shumilla JA, Kumar S, Maldve R, Pandey SC (2004) Ethanol effects on cell signaling mechanisms. Alcohol Clin Exp Res 28:217–227PubMedGoogle Scholar
  12. 12.
    Harris RA, Trudell JR, Mihic SJ (2008) Ethanol’s molecular targets. Sci Signal 1, re7Google Scholar
  13. 13.
    Heilig M, Koob GF (2007) A key role for corticotropin-releasing factor in alcohol dependence. Trends Neurosci 30:399–406PubMedGoogle Scholar
  14. 14.
    Thorsell A (2008) Central neuropeptide Y in anxiety- and stress-related behavior and in ethanol intake. Ann N Y Acad Sci 1148:136–140PubMedCrossRefGoogle Scholar
  15. 15.
    Davis MI (2008) Ethanol-BDNF interactions: still more questions than answers. Pharmacol Ther 118:36–57PubMedGoogle Scholar
  16. 16.
    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 28:2589–2600PubMedGoogle Scholar
  17. 17.
    Shukla SD, Velazquez J, French SW, Lu SC, Ticku MK, Zakhari S (2008) Emerging role of epigenetics in the actions of alcohol. Alcohol Clin Exp Res 32:1525–1534PubMedGoogle Scholar
  18. 18.
    Pandey SC, Ugale R, Zhang H, Tang L, Prakash A (2008) Brain chromatin remodeling: a novel mechanism of alcoholism. J Neurosci 28:3729–3737PubMedGoogle Scholar
  19. 19.
    Abel T, Kandel E (1998) Positive and negative regulatory mechanisms that mediate long-term memory storage. Brain Res Brain Res Rev 26:360–378PubMedGoogle Scholar
  20. 20.
    Alberini CM (2009) Transcription factors in long-term memory and synaptic plasticity. Physiol Rev 89:121–145PubMedGoogle Scholar
  21. 21.
    Shaywitz AJ, Greenberg ME (1999) CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu Rev Biochem 68:821–861PubMedGoogle Scholar
  22. 22.
    Chrivia JC, Kwok RP, Lamb N, Hagiwara M, Montminy MR, Goodman RH (1993) Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 365:855–859PubMedGoogle Scholar
  23. 23.
    Li TK, Lumeng L, Doolittle DP (1993) Selective breeding for alcohol preference and associated responses. Behav Genet 23:163–170PubMedGoogle Scholar
  24. 24.
    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 23:1425–1434PubMedGoogle Scholar
  25. 25.
    Bell RL, Rodd ZA, Lumeng L, Murphy JM, McBride WJ (2006) The alcohol-preferring P rat and animal models of excessive alcohol drinking. Addict Biol 11:270–288PubMedGoogle Scholar
  26. 26.
    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 115:2762–2773PubMedGoogle Scholar
  27. 27.
    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 24:5022–5030PubMedGoogle Scholar
  28. 28.
    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 27:396–409PubMedGoogle Scholar
  29. 29.
    Yang X, Horn K, Wand GS (1998) Chronic ethanol exposure impairs phosphorylation of CREB and CRE-binding activity in rat striatum. Alcohol Clin Exp Res 22:382–390PubMedGoogle Scholar
  30. 30.
    Yang X, Diehl AM, Wand GS (1996) Ethanol exposure alters the phosphorylation of cyclic AMP responsive element binding protein and cyclic AMP responsive element binding activity in rat cerebellum. J Pharmacol Exp Ther 278:338–346PubMedGoogle Scholar
  31. 31.
    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 70:224–232PubMedGoogle Scholar
  32. 32.
    Pandey SC, Zhang D, Mittal N, Nayyar D (1999) Potential role of the gene transcription factor cyclic AMP-responsive element binding protein in ethanol withdrawal-related anxiety. J Pharmacol Exp Ther 288:866–878PubMedGoogle Scholar
  33. 33.
    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 296:857–868PubMedGoogle Scholar
  34. 34.
    Li J, Li YH, Yuan XR (2003) Changes of phosphorylation of cAMP response element binding protein in rat nucleus accumbens after chronic ethanol intake: naloxone reversal. Acta Pharmacol Sin 24:930–936PubMedGoogle Scholar
  35. 35.
    Misra K, Roy A, Pandey SC (2001) Effects of voluntary ethanol intake on the expression of Ca2+/calmodulin-dependent protein kinase IV and on CREB expression and phosphorylation in the rat nucleus accumbens. Neuroreport 12:4133–4137PubMedGoogle Scholar
  36. 36.
    Misra K, Pandey SC (2003) Differences in basal levels of CREB and NPY in nucleus accumbens regions between C57BL/6 and DBA/2 mice differing in inborn alcohol drinking behavior. J Neurosci Res 74:967–975PubMedGoogle Scholar
  37. 37.
    Belknap JK, Crabbe JC, Young ER (1993) Voluntary consumption of ethanol in 15 inbred mouse strains. Psychopharmacology (Berl) 112:503–510Google Scholar
  38. 38.
    Wang Y, Ghezzi A, Yin JC, Atkinson NS (2009) CREB regulation of BK channel gene expression underlies rapid drug tolerance. Genes Brain Behav 8:369–376PubMedGoogle Scholar
  39. 39.
    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 27:1220–1225PubMedGoogle Scholar
  40. 40.
    Zou J, Crews F (2006) CREB and NF-κB transcription factors regulate sensitivity to excitotoxic and oxidative stress induced neuronal cell death. Cell Mol Neurobiol 26:385–405PubMedGoogle Scholar
  41. 41.
    Chandler LJ, Sutton G (2005) Acute ethanol inhibits extracellular signal-regulated kinase, protein kinase B, and adenosine 3′:5′-cyclic monophosphate response element binding protein activity in an age- and brain region-specific manner. Alcohol Clin Exp Res 29:672–682PubMedGoogle Scholar
  42. 42.
    Acquaah-Mensah GK, Misra V, Biswal S (2006) Ethanol sensitivity: a central role for CREB transcription regulation in the cerebellum. BMC Genomics 7:308PubMedGoogle Scholar
  43. 43.
    Narahashi T, Kuriyama K, Illes P, Wirkner K, Fischer W, Muhlberg K, Scheibler P, Allgaier C, Minami K, Lovinger D, Lallemand F, Ward RJ, DeWitte P, Itatsu T, Takei Y, Oide H, Hirose M, Wang XE, Watanabe S, Tateyama M, Ochi R, Sato N (2001) Neuroreceptors and ion channels as targets of alcohol. Alcohol Clin Exp Res 25:182S–188SPubMedGoogle Scholar
  44. 44.
    Vengeliene V, Bilbao A, Molander A, Spanagel R (2008) Neuropharmacology of alcohol addiction. Br J Pharmacol 154:299–315PubMedGoogle Scholar
  45. 45.
    Lovinger DM, White G, Weight FF (1989) Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science 243:1721–1724PubMedGoogle Scholar
  46. 46.
    Nestoros JN (1980) Ethanol specifically potentiates GABA-mediated neurotransmission in feline cerebral cortex. Science 209:708–710PubMedGoogle Scholar
  47. 47.
    Peoples RW, Weight FF (1995) Cutoff in potency implicates alcohol inhibition of n-methyl-d-aspartate receptors in alcohol intoxication. Proc Natl Acad Sci USA 92:2825–2829PubMedGoogle Scholar
  48. 48.
    Ren H, Salous AK, Paul JM, Lipsky RH, Peoples RW (2007) Mutations at F637 in the NMDA receptor NR2A subunit M3 domain influence agonist potency, ion channel gating and alcohol action. Br J Pharmacol 151:749–757PubMedGoogle Scholar
  49. 49.
    Ronald KM, Mirshahi T, Woodward JJ (2001) Ethanol inhibition of n-methyl-d-aspartate receptors is reduced by site-directed mutagenesis of a transmembrane domain phenylalanine residue. J Biol Chem 276:44729–44735PubMedGoogle Scholar
  50. 50.
    Paoletti P, Neyton J (2007) NMDA receptor subunits: function and pharmacology. Curr Opin Pharmacol 7:39–47PubMedGoogle Scholar
  51. 51.
    Smothers CT, Clayton R, Blevins T, Woodward JJ (2001) Ethanol sensitivity of recombinant human n-methyl-d-aspartate receptors. Neurochem Int 38:333–340PubMedGoogle Scholar
  52. 52.
    Nagy J (2004) The NR2B subtype of NMDA receptor: a potential target for the treatment of alcohol dependence. Curr Drug Targets CNS Neurol Disord 3:169–179PubMedGoogle Scholar
  53. 53.
    Rani CS, Qiang M, Ticku MK (2005) Potential role of cAMP response element-binding protein in ethanol-induced n-methyl-d-aspartate receptor 2B subunit gene transcription in fetal mouse cortical cells. Mol Pharmacol 67:2126–2136PubMedGoogle Scholar
  54. 54.
    Wang JQ, Fibuch EE, Mao L (2007) Regulation of mitogen-activated protein kinases by glutamate receptors. J Neurochem 100:1–11PubMedGoogle Scholar
  55. 55.
    Netzeband JG, Gruol DL (1995) Modulatory effects of acute ethanol on metabotropic glutamate responses in cultured Purkinje neurons. Brain Res 688:105–113PubMedGoogle Scholar
  56. 56.
    Minami K, Gereau RW 4th, Minami M, Heinemann SF, Harris RA (1998) Effects of ethanol and anesthetics on type 1 and 5 metabotropic glutamate receptors expressed in Xenopus laevis oocytes. Mol Pharmacol 53:148–156PubMedGoogle Scholar
  57. 57.
    Gass JT, Olive MF (2009) Role of protein kinase C epsilon (PKCε) in the reduction of ethanol reinforcement due to mGluR5 antagonism in the nucleus accumbens shell. Psychopharmacology (Berl) 204:587–597Google Scholar
  58. 58.
    Schroeder JP, Overstreet DH, Hodge CW (2005) The mGluR5 antagonist MPEP decreases operant ethanol self-administration during maintenance and after repeated alcohol deprivations in alcohol-preferring (P) rats. Psychopharmacology (Berl) 179:262–270Google Scholar
  59. 59.
    McMillen BA, Crawford MS, Kulers CM, Williams HL (2005) Effects of a metabotropic, mGlu5, glutamate receptor antagonist on ethanol consumption by genetic drinking rats. Alcohol Alcohol 40:494–497PubMedGoogle Scholar
  60. 60.
    Hodge CW, Miles MF, Sharko AC, Stevenson RA, Hillmann JR, Lepoutre V, Besheer J, Schroeder JP (2006) The mGluR5 antagonist MPEP selectively inhibits the onset and maintenance of ethanol self-administration in C57BL/6J mice. Psychopharmacology (Berl) 183:429–438Google Scholar
  61. 61.
    Mermelstein PG, Bito H, Deisseroth K, Tsien RW (2000) Critical dependence of cAMP response element-binding protein phosphorylation on L-type calcium channels supports a selective response to EPSPs in preference to action potentials. J Neurosci 20:266–273PubMedGoogle Scholar
  62. 62.
    Mullikin-Kilpatrick D, Mehta ND, Hildebrandt JD, Treistman SN (1995) Gi is involved in ethanol inhibition of l-type calcium channels in undifferentiated but not differentiated PC-12 cells. Mol Pharmacol 47:997–1005PubMedGoogle Scholar
  63. 63.
    Katsura M, Shibasaki M, Hayashida S, Torigoe F, Tsujimura A, Ohkuma S (2006) Increase in expression of α1 and α2/δ1 subunits of l-type high voltage-gated calcium channels after sustained ethanol exposure in cerebral cortical neurons. J Pharmacol Sci 102:221–230PubMedGoogle Scholar
  64. 64.
    Walter HJ, McMahon T, Dadgar J, Wang D, Messing RO (2000) Ethanol regulates calcium channel subunits by protein kinase C δ-dependent and -independent mechanisms. J Biol Chem 275:25717–25722PubMedGoogle Scholar
  65. 65.
    Gardell LR, Reid LD, Boedeker KL, Liakos TM, Hubbell CL (1997) Isradipine and naltrexone in combination with isradipine interact with a period of abstinence to reduce rats’ intakes of an alcoholic beverage. Alcohol Clin Exp Res 21:1592–1598PubMedGoogle Scholar
  66. 66.
    Rezvani AH, Janowsky DS (1990) Decreased alcohol consumption by verapamil in alcohol preferring rats. Prog Neuropsychopharmacol Biol Psychiatry 14:623–631PubMedGoogle Scholar
  67. 67.
    De Beun R, Schneider R, Klein A, Lohmann A, De Vry J (1996) Effects of nimodipine and other calcium channel antagonists in alcohol-preferring AA rats. Alcohol 13:263–271PubMedGoogle Scholar
  68. 68.
    Hatta S, Saito T, Ohshika H (1994) Effects of ethanol on the function of G proteins in rat cerebral cortex membranes. Alcohol Alcohol Suppl 29:45–51PubMedGoogle Scholar
  69. 69.
    Mochly-Rosen D, Chang FH, Cheever L, Kim M, Diamond I, Gordon AS (1988) Chronic ethanol causes heterologous desensitization of receptors by reducing αs messenger RNA. Nature 333:848–850PubMedGoogle Scholar
  70. 70.
    Tabakoff B, Whelan JP, Ovchinnikova L, Nhamburo P, Yoshimura M, Hoffman PL (1995) Quantitative changes in G proteins do not mediate ethanol-induced downregulation of adenylyl cyclase in mouse cerebral cortex. Alcohol Clin Exp Res 19:187–194PubMedGoogle Scholar
  71. 71.
    Yoshimura M, Tabakoff B (1995) Selective effects of ethanol on the generation of cAMP by particular members of the adenylyl cyclase family. Alcohol Clin Exp Res 19:1435–1440PubMedGoogle Scholar
  72. 72.
    Yoshimura M, Pearson S, Kadota Y, Gonzalez CE (2006) Identification of ethanol responsive domains of adenylyl cyclase. Alcohol Clin Exp Res 30:1824–1832PubMedGoogle Scholar
  73. 73.
    Constantinescu A, Diamond I, Gordon AS (1999) Ethanol-induced translocation of cAMP-dependent protein kinase to the nucleus. Mechanism and functional consequences. J Biol Chem 274:26985–26991PubMedGoogle Scholar
  74. 74.
    Ron D, Jurd R (2005) The “ups and downs” of signaling cascades in addiction. Sci STKE 2005, re14Google Scholar
  75. 75.
    Lee AM, Messing RO (2008) Protein kinases and addiction. Ann N Y Acad Sci 1141:22–57PubMedGoogle Scholar
  76. 76.
    Wayman GA, Lee YS, Tokumitsu H, Silva A, Soderling TR (2008) Calmodulin-kinases: modulators of neuronal development and plasticity. Neuron 59:914–931PubMedGoogle Scholar
  77. 77.
    Li J, Bian WL, Xie GQ, Cui SZ, Wu ML, Li YH, Que LL, Yuan XR (2008) Chronic ethanol intake-induced changes in open-field behavior and calcium/calmodulin-dependent protein kinase IV expression in nucleus accumbens of rats: naloxone reversal. Acta Pharmacol Sin 29:646–652PubMedGoogle Scholar
  78. 78.
    Mahadev K, Chetty CS, Vemuri MC (2001) Effect of prenatal and postnatal ethanol exposure on Ca2+/calmodulin-dependent protein kinase II in rat cerebral cortex. Alcohol 23:183–188PubMedGoogle Scholar
  79. 79.
    Liu J, Asuncion-Chin M, Liu P, Dopico AM (2006) CaM kinase II phosphorylation of slo Thr107 regulates activity and ethanol responses of BK channels. Nat Neurosci 9:41–49PubMedGoogle Scholar
  80. 80.
    Xu M, Chandler LJ, Woodward JJ (2008) Ethanol inhibition of recombinant NMDA receptors is not altered by coexpression of CaMKII-α or CaMKII-β. Alcohol 42:425–432PubMedGoogle Scholar
  81. 81.
    Brandon EP, Idzerda RL, McKnight GS (1997) PKA isoforms, neural pathways, and behaviour: making the connection. Curr Opin Neurobiol 7:397–403PubMedGoogle Scholar
  82. 82.
    Dohrman DP, Diamond I, Gordon AS (1996) Ethanol causes translocation of cAMP-dependent protein kinase catalytic subunit to the nucleus. Proc Natl Acad Sci USA 93:10217–10221PubMedGoogle Scholar
  83. 83.
    Misra K, Pandey SC (2006) The decreased cyclic-AMP dependent-protein kinase A function in the nucleus accumbens: a role in alcohol drinking but not in anxiety-like behaviors in rats. Neuropsychopharmacology 31:1406–1419PubMedGoogle Scholar
  84. 84.
    Yao L, Arolfo MP, Dohrman DP, Jiang Z, Fan P, Fuchs S, Janak PH, Gordon AS, Diamond I (2002) βγ Dimers mediate synergy of dopamine D2 and adenosine A2 receptor-stimulated PKA signaling and regulate ethanol consumption. Cell 109:733–743PubMedGoogle Scholar
  85. 85.
    Zhang H, Pandey SC (2003) Effects of PKA modulation on the expression of neuropeptide Y in rat amygdaloid structures during ethanol withdrawal. Peptides 24:1397–1402PubMedGoogle Scholar
  86. 86.
    Lai CC, Kuo TI, Lin HH (2007) The role of protein kinase A in acute ethanol-induced neurobehavioral actions in rats. Anesth Analg 105:89–96PubMedGoogle Scholar
  87. 87.
    Thiele TE, Willis B, Stadler J, Reynolds JG, Bernstein IL, McKnight GS (2000) High ethanol consumption and low sensitivity to ethanol-induced sedation in protein kinase A-mutant mice. J Neurosci 20:RC75PubMedGoogle Scholar
  88. 88.
    Repunte-Canonigo V, Lutjens R, van der Stap LD, Sanna PP (2007) Increased expression of protein kinase A inhibitor α (PKI-α) and decreased PKA-regulated genes in chronic intermittent alcohol exposure. Brain Res 1138:48–56PubMedGoogle Scholar
  89. 89.
    Atkins CM, Selcher JC, Petraitis JJ, Trzaskos JM, Sweatt JD (1998) The MAPK cascade is required for mammalian associative learning. Nat Neurosci 1:602–609PubMedGoogle Scholar
  90. 90.
    Thomas GM, Huganir RL (2004) MAPK cascade signalling and synaptic plasticity. Nat Rev Neurosci 5:173–183PubMedGoogle Scholar
  91. 91.
    Sanna PP, Simpson C, Lutjens R, Koob G (2002) ERK regulation in chronic ethanol exposure and withdrawal. Brain Res 948:186–191PubMedGoogle Scholar
  92. 92.
    Kalluri HS, Ticku MK (2003) Regulation of ERK phosphorylation by ethanol in fetal cortical neurons. Neurochem Res 28:765–769PubMedGoogle Scholar
  93. 93.
    Carnicella S, Kharazia V, Jeanblanc J, Janak PH, Ron D (2008) GDNF is a fast-acting potent inhibitor of alcohol consumption and relapse. Proc Natl Acad Sci USA 105:8114–8119PubMedGoogle Scholar
  94. 94.
    Pandey SC, Zhang H, Roy A, Misra K (2006) Central and medial amygdaloid brain-derived neurotrophic factor signaling plays a critical role in alcohol-drinking and anxiety-like behaviors. J Neurosci 26:8320–8331PubMedGoogle Scholar
  95. 95.
    Xie GQ, Wang SJ, Li J, Cui SZ, Zhou R, Chen L, Yuan XR (2009) Ethanol attenuates the HFS-induced, ERK-mediated LTP in a dose-dependent manner in rat striatum. Alcohol Clin Exp Res 33:121–128PubMedGoogle Scholar
  96. 96.
    Roberto M, Nelson TE, Ur CL, Brunelli M, Sanna PP, Gruol DL (2003) The transient depression of hippocampal CA1 LTP induced by chronic intermittent ethanol exposure is associated with an inhibition of the MAP kinase pathway. Eur J Neurosci 17:1646–1654PubMedGoogle Scholar
  97. 97.
    Kuczewski N, Porcher C, Lessmann V, Medina I, Gaiarsa JL (2009) Activity-dependent dendritic release of BDNF and biological consequences. Mol Neurobiol 39:37–49PubMedGoogle Scholar
  98. 98.
    Horch HW (2004) Local effects of BDNF on dendritic growth. Rev Neurosci 15:117–129PubMedGoogle Scholar
  99. 99.
    Maisonpierre PC, Belluscio L, Friedman B, Alderson RF, Wiegand SJ, Furth ME, Lindsay RM, Yancopoulos GD (1990) NT-3, BDNF, and NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expression. Neuron 5:501–509PubMedGoogle Scholar
  100. 100.
    Messaoudi E, Ying SW, Kanhema T, Croll SD, Bramham CR (2002) Brain-derived neurotrophic factor triggers transcription-dependent, late phase long-term potentiation in vivo. J Neurosci 22:7453–7461PubMedGoogle Scholar
  101. 101.
    Poo MM (2001) Neurotrophins as synaptic modulators. Nat Rev Neurosci 2:24–32PubMedGoogle Scholar
  102. 102.
    Reichardt LF (2006) Neurotrophin-regulated signalling pathways. Philos Trans R Soc Lond B 361:1545–1564Google Scholar
  103. 103.
    Pizzorusso T, Ratto GM, Putignano E, Maffei L (2000) Brain-derived neurotrophic factor causes cAMP response element-binding protein phosphorylation in absence of calcium increases in slices and cultured neurons from rat visual cortex. J Neurosci 20:2809–2816PubMedGoogle Scholar
  104. 104.
    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 20:709–726PubMedGoogle Scholar
  105. 105.
    Deogracias R, Espliguero G, Iglesias T, Rodriguez-Pena A (2004) Expression of the neurotrophin receptor TrkB is regulated by the cAMP/CREB pathway in neurons. Mol Cell Neurosci 26:470–480PubMedGoogle Scholar
  106. 106.
    Tada T, Sheng M (2006) Molecular mechanisms of dendritic spine morphogenesis. Curr Opin Neurobiol 16:95–101PubMedGoogle Scholar
  107. 107.
    Ying SW, Futter M, Rosenblum K, Webber MJ, Hunt SP, Bliss TV, Bramham CR (2002) Brain-derived neurotrophic factor induces long-term potentiation in intact adult hippocampus: requirement for ERK activation coupled to CREB and upregulation of Arc synthesis. J Neurosci 22:1532–1540PubMedGoogle Scholar
  108. 108.
    Bramham CR, Worley PF, Moore MJ, Guzowski JF (2008) The immediate early gene Arc/Arg3.1: regulation, mechanisms, and function. J Neurosci 28:11760–11767PubMedGoogle Scholar
  109. 109.
    Messaoudi E, Kanhema T, Soule J, Tiron A, Dagyte G, da Silva B, Bramham CR (2007) Sustained Arc/Arg3.1 synthesis controls long-term potentiation consolidation through regulation of local actin polymerization in the dentate gyrus in vivo. J Neurosci 27:10445–10455PubMedGoogle Scholar
  110. 110.
    Huang F, Chotiner JK, Steward O (2007) Actin polymerization and ERK phosphorylation are required for Arc/Arg3.1 mRNA targeting to activated synaptic sites on dendrites. J Neurosci 27:9054–9067PubMedGoogle Scholar
  111. 111.
    Soule J, Messaoudi E, Bramham CR (2006) Brain-derived neurotrophic factor and control of synaptic consolidation in the adult brain. Biochem Soc Trans 34:600–604PubMedGoogle Scholar
  112. 112.
    Pak DT, Yang S, Rudolph-Correia S, Kim E, Sheng M (2001) Regulation of dendritic spine morphology by SPAR, a PSD-95-associated RapGAP. Neuron 31:289–303PubMedGoogle Scholar
  113. 113.
    Vickers CA, Stephens B, Bowen J, Arbuthnott GW, Grant SG, Ingham CA (2006) Neurone specific regulation of dendritic spines in vivo by post synaptic density 95 protein (PSD-95). Brain Res 1090:89–98PubMedGoogle Scholar
  114. 114.
    Starkman BG, Pandey SC (2007) Brain-derived neurotrophic factor and mental illness: an epigenetic approach. Proc Natl Acad Sci India 77(B):105–113Google Scholar
  115. 115.
    Angelucci F, Brene S, Mathe AA (2005) BDNF in schizophrenia, depression and corresponding animal models. Mol Psychiatry 10:345–352PubMedGoogle Scholar
  116. 116.
    Jeanblanc J, He DY, McGough NN, Logrip ML, Phamluong K, Janak PH, Ron D (2006) The dopamine D3 receptor is part of a homeostatic pathway regulating ethanol consumption. J Neurosci 26:1457–1464PubMedGoogle Scholar
  117. 117.
    Hensler JG, Ladenheim EE, Lyons WE (2003) Ethanol consumption and serotonin-1A (5-HT1A) receptor function in heterozygous BDNF (+/−) mice. J Neurochem 85:1139–1147PubMedGoogle Scholar
  118. 118.
    MacLennan AJ, Lee N, Walker DW (1995) Chronic ethanol administration decreases brain-derived neurotrophic factor gene expression in the rat hippocampus. Neurosci Lett 197:105–108PubMedGoogle Scholar
  119. 119.
    Kerns RT, Ravindranathan A, Hassan S, Cage MP, York T, Sikela JM, Williams RW, Miles MF (2005) Ethanol-responsive brain region expression networks: implications for behavioral responses to acute ethanol in DBA/2J versus C57BL/6J mice. J Neurosci 25:2255–2266PubMedGoogle Scholar
  120. 120.
    Sakai R, Ukai W, Sohma H, Hashimoto E, Yamamoto M, Ikeda H, Saito T (2005) Attenuation of brain derived neurotrophic factor (BDNF) by ethanol and cytoprotective effect of exogenous BDNF against ethanol damage in neuronal cells. J Neural Transm 112:1005–1013PubMedGoogle Scholar
  121. 121.
    McGough NN, He DY, Logrip ML, Jeanblanc J, Phamluong K, Luong K, Kharazia V, Janak PH, Ron D (2004) RACK1 and brain-derived neurotrophic factor: a homeostatic pathway that regulates alcohol addiction. J Neurosci 24:10542–10552PubMedGoogle Scholar
  122. 122.
    Prakash A, Zhang H, Pandey SC (2008) Innate differences in the expression of brain-derived neurotrophic factor in the regions within the extended amygdala between alcohol preferring and nonpreferring rats. Alcohol Clin Exp Res 32:909–920PubMedGoogle Scholar
  123. 123.
    Yan QS, Feng MJ, Yan SE (2005) Different expression of brain-derived neurotrophic factor in the nucleus accumbens of alcohol-preferring (P) and -nonpreferring (NP) rats. Brain Res 1035:215–218PubMedGoogle Scholar
  124. 124.
    Lescaudron L, Jaffard R, Verna A (1989) Modifications in number and morphology of dendritic spines resulting from chronic ethanol consumption and withdrawal: a Golgi study in the mouse anterior and posterior hippocampus. Exp Neurol 106:156–163PubMedGoogle Scholar
  125. 125.
    Lee K, Dunwiddie T, Deitrich R, Lynch G, Hoffer B (1981) Chronic ethanol consumption and hippocampal neuron dendritic spines: a morphometric and physiological analysis. Exp Neurol 71:541–549PubMedGoogle Scholar
  126. 126.
    Riley JN, Walker DW (1978) Morphological alterations in hippocampus after long-term alcohol consumption in mice. Science 201:646–648PubMedGoogle Scholar
  127. 127.
    Chandler LJ (2003) Ethanol and brain plasticity: receptors and molecular networks of the postsynaptic density as targets of ethanol. Pharmacol Ther 99:311–326PubMedGoogle Scholar
  128. 128.
    Zhou FC, Anthony B, Dunn KW, Lindquist WB, Xu ZC, Deng P (2007) Chronic alcohol drinking alters neuronal dendritic spines in the brain reward center nucleus accumbens. Brain Res 1134:148–161PubMedGoogle Scholar
  129. 129.
    Moonat S, Sakharkar A, Zhang H, Pandey SC (2009) Effects of acute ethanol exposure on amygdaloid dendritic morphology and anxiety-like behaviors in P and NP rats. J Neurochem 108(Suppl 1):96–97Google Scholar
  130. 130.
    Carpenter-Hyland EP, Chandler LJ (2006) Homeostatic plasticity during alcohol exposure promotes enlargement of dendritic spines. Eur J Neurosci 24:3496–3506PubMedGoogle Scholar
  131. 131.
    Halford JC, Cooper GD, Dovey TM (2004) The pharmacology of human appetite expression. Curr Drug Targets 5:221–240PubMedGoogle Scholar
  132. 132.
    Hansel DE, Eipper BA, Ronnett GV (2001) Regulation of olfactory neurogenesis by amidated neuropeptides. J Neurosci Res 66:1–7PubMedGoogle Scholar
  133. 133.
    Sajdyk TJ, Shekhar A, Gehlert DR (2004) Interactions between NPY and CRF in the amygdala to regulate emotionality. Neuropeptides 38:225–234PubMedGoogle Scholar
  134. 134.
    Fetissov SO, Kopp J, Hokfelt T (2004) Distribution of NPY receptors in the hypothalamus. Neuropeptides 38:175–188PubMedGoogle Scholar
  135. 135.
    Sheriff S, Qureshy AF, Chance WT, Kasckow JW, Balasubramaniam A (2002) Predominant role by CaM kinase in NPY Y1 receptor signaling: involvement of CREB. Peptides 23:87–96PubMedGoogle Scholar
  136. 136.
    Chance WT, Sheriff S, Peng F, Balasubramaniam A (2000) Antagonism of NPY-induced feeding by pretreatment with cyclic AMP response element binding protein antisense oligonucleotide. Neuropeptides 34:167–172PubMedGoogle Scholar
  137. 137.
    Higuchi H, Yang HY, Sabol SL (1988) Rat neuropeptide Y precursor gene expression. mRNA structure, tissue distribution, and regulation by glucocorticoids, cyclic AMP, and phorbol ester. J Biol Chem 263:6288–6295PubMedGoogle Scholar
  138. 138.
    Sheriff S, Dayal R, Kasckow J, Regmi A, Chance W, Fischer J, Balasubramaniam A (1998) NPY upregulates genes containing cyclic AMP response element in human neuroblastoma cell lines bearing Y1 and Y2 receptors: involvement of CREB. Regul Pept 75–76:309–318PubMedGoogle Scholar
  139. 139.
    Hwang BH, Zhang JK, Ehlers CL, Lumeng L, Li TK (1999) Innate differences of neuropeptide Y (NPY) in hypothalamic nuclei and central nucleus of the amygdala between selectively bred rats with high and low alcohol preference. Alcohol Clin Exp Res 23:1023–1030PubMedGoogle Scholar
  140. 140.
    Roy A, Pandey SC (2002) The decreased cellular expression of neuropeptide Y protein in rat brain structures during ethanol withdrawal after chronic ethanol exposure. Alcohol Clin Exp Res 26:796–803PubMedGoogle Scholar
  141. 141.
    Thiele TE, Marsh DJ, Ste Marie L, Bernstein IL, Palmiter RD (1998) Ethanol consumption and resistance are inversely related to neuropeptide Y levels. Nature 396:366–369PubMedGoogle Scholar
  142. 142.
    Palmiter RD, Erickson JC, Hollopeter G, Baraban SC, Schwartz MW (1998) Life without neuropeptide Y. Recent Prog Horm Res 53:163–199PubMedGoogle Scholar
  143. 143.
    Heilig M, Soderpalm B, Engel JA, Widerlov E (1989) Centrally administered neuropeptide Y (NPY) produces anxiolytic-like effects in animal anxiety models. Psychopharmacology (Berl) 98:524–529Google Scholar
  144. 144.
    Heilig M (1995) Antisense inhibition of neuropeptide Y (NPY)-Y1 receptor expression blocks the anxiolytic-like action of NPY in amygdala and paradoxically increases feeding. Regul Pept 59:201–205PubMedGoogle Scholar
  145. 145.
    Thiele TE, Koh MT, Pedrazzini T (2002) Voluntary alcohol consumption is controlled via the neuropeptide Y Y1 receptor. J Neurosci 22(RC208):1–6Google Scholar
  146. 146.
    Rimondini R, Thorsell A, Heilig M (2005) Suppression of ethanol self-administration by the neuropeptide Y (NPY) Y2 receptor antagonist BIIE0246: evidence for sensitization in rats with a history of dependence. Neurosci Lett 375:129–133PubMedGoogle Scholar
  147. 147.
    Thiele TE, Naveilhan P, Ernfors P (2004) Assessment of ethanol consumption and water drinking by NPY Y2 receptor knockout mice. Peptides 25:975–983PubMedGoogle Scholar
  148. 148.
    Schroeder JP, Iller KA, Hodge CW (2003) Neuropeptide-Y Y5 receptors modulate the onset and maintenance of operant ethanol self-administration. Alcohol Clin Exp Res 27:1912–1920PubMedGoogle Scholar
  149. 149.
    Katner SN, Slawecki CJ, Ehlers CL (2002) Neuropeptide Y administration into the amygdala does not affect ethanol consumption. Alcohol 28:29–38PubMedGoogle Scholar
  150. 150.
    Badia-Elder NE, Stewart RB, Powrozek TA, Roy KF, Murphy JM, Li TK (2001) Effect of neuropeptide Y (NPY) on oral ethanol intake in Wistar, alcohol-preferring (P), and -nonpreferring (NP) rats. Alcohol Clin Exp Res 25:386–390PubMedGoogle Scholar
  151. 151.
    Primeaux SD, Wilson SP, Bray GA, York DA, Wilson MA (2006) Overexpression of neuropeptide Y in the central nucleus of the amygdala decreases ethanol self-administration in “anxious” rats. Alcohol Clin Exp Res 30:791–801PubMedGoogle Scholar
  152. 152.
    Thorsell A, Repunte-Canonigo V, O’Dell LE, Chen SA, King AR, Lekic D, Koob GF, Sanna PP (2007) Viral vector-induced amygdala NPY overexpression reverses increased alcohol intake caused by repeated deprivations in Wistar rats. Brain 130:1330–1337PubMedGoogle Scholar
  153. 153.
    Gilpin NW, Stewart RB, Badia-Elder NE (2008) Neuropeptide Y administration into the amygdala suppresses ethanol drinking in alcohol-preferring (P) rats following multiple deprivations. Pharmacol Biochem Behav 90:470–474PubMedGoogle Scholar
  154. 154.
    Gilpin NW, Misra K, Koob GF (2008) Neuropeptide Y in the central nucleus of the amygdala suppresses dependence-induced increases in alcohol drinking. Pharmacol Biochem Behav 90:475–480PubMedGoogle Scholar
  155. 155.
    Perrin MH, Vale WW (1999) Corticotropin releasing factor receptors and their ligand family. Ann N Y Acad Sci 885:312–328PubMedCrossRefGoogle Scholar
  156. 156.
    Gray TS (1993) Amygdaloid CRF pathways. Role in autonomic, neuroendocrine, and behavioral responses to stress. Ann N Y Acad Sci 697:53–60PubMedGoogle Scholar
  157. 157.
    Koob GF, Heinrichs SC (1999) A role for corticotropin releasing factor and urocortin in behavioral responses to stressors. Brain Res 848:141–152PubMedGoogle Scholar
  158. 158.
    Yao M, Stenzel-Poore M, Denver RJ (2007) Structural and functional conservation of vertebrate corticotropin-releasing factor genes: evidence for a critical role for a conserved cyclic AMP response element. Endocrinology 148:2518–2531PubMedGoogle Scholar
  159. 159.
    Rassnick S, Heinrichs SC, Britton KT, Koob GF (1993) Microinjection of a corticotropin-releasing factor antagonist into the central nucleus of the amygdala reverses anxiogenic-like effects of ethanol withdrawal. Brain Res 605:25–32PubMedGoogle Scholar
  160. 160.
    Funk CK, O’Dell LE, Crawford EF, Koob GF (2006) Corticotropin-releasing factor within the central nucleus of the amygdala mediates enhanced ethanol self-administration in withdrawn, ethanol-dependent rats. J Neurosci 26:11324–11332PubMedGoogle Scholar
  161. 161.
    Finn DA, Snelling C, Fretwell AM, Tanchuck MA, Underwood L, Cole M, Crabbe JC, Roberts AJ (2007) Increased drinking during withdrawal from intermittent ethanol exposure is blocked by the CRF receptor antagonist D-Phe-CRF(12-41). Alcohol Clin Exp Res 31:939–949PubMedGoogle Scholar
  162. 162.
    Funk CK, Koob GF (2007) A CRF2 agonist administered into the central nucleus of the amygdala decreases ethanol self-administration in ethanol-dependent rats. Brain Res 1155:172–178PubMedGoogle Scholar
  163. 163.
    Merlo Pich E, Lorang M, Yeganeh M, Rodriguez de Fonseca F, Raber J, Koob GF, Weiss F (1995) Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis. J Neurosci 15:5439–5447PubMedGoogle Scholar
  164. 164.
    Richter RM, Zorrilla EP, Basso AM, Koob GF, Weiss F (2000) Altered amygdalar CRF release and increased anxiety-like behavior in Sardinian alcohol-preferring rats: a microdialysis and behavioral study. Alcohol Clin Exp Res 24:1765–1772PubMedGoogle Scholar
  165. 165.
    Hwang BH, Stewart R, Zhang JK, Lumeng L, Li TK (2004) Corticotropin-releasing factor gene expression is down-regulated in the central nucleus of the amygdala of alcohol-preferring rats which exhibit high anxiety: a comparison between rat lines selectively bred for high and low alcohol preference. Brain Res 1026:143–150PubMedGoogle Scholar
  166. 166.
    Ehlers CL, Chaplin RI, Wall TL, Lumeng L, Li TK, Owens MJ, Nemeroff CB (1992) Corticotropin releasing factor (CRF): studies in alcohol preferring and non-preferring rats. Psychopharmacology (Berl) 106:359–364Google Scholar
  167. 167.
    Nie Z, Schweitzer P, Roberts AJ, Madamba SG, Moore SD, Siggins GR (2004) Ethanol augments GABAergic transmission in the central amygdala via CRF1 receptors. Science 303:1512–1514PubMedGoogle Scholar
  168. 168.
    Bajo M, Cruz MT, Siggins GR, Messing R, Roberto M (2008) Protein kinase C epsilon mediation of CRF- and ethanol-induced GABA release in central amygdala. Proc Natl Acad Sci USA 105:8410–8415PubMedGoogle Scholar
  169. 169.
    Valdez GR, Koob GF (2004) Allostasis and dysregulation of corticotropin-releasing factor and neuropeptide Y systems: implications for the development of alcoholism. Pharmacol Biochem Behav 79:671–689PubMedGoogle Scholar
  170. 170.
    Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074–1080PubMedGoogle Scholar
  171. 171.
    Smith MM (1991) Histone structure and function. Curr Opin Cell Biol 3:429–437PubMedGoogle Scholar
  172. 172.
    Tsankova N, Renthal W, Kumar A, Nestler EJ (2007) Epigenetic regulation in psychiatric disorders. Nat Rev Neurosci 8:355–367PubMedGoogle Scholar
  173. 173.
    Saetrom P, Snove O Jr, Rossi JJ (2007) Epigenetics and microRNAs. Pediatr Res 61:17R–23RPubMedGoogle Scholar
  174. 174.
    Strahl BD, Allis CD (2000) The language of covalent histone modifications. Nature 403:41–45PubMedGoogle Scholar
  175. 175.
    Chandramohan Y, Droste SK, Arthur JS, Reul JM (2008) The forced swimming-induced behavioural immobility response involves histone H3 phospho-acetylation and c-Fos induction in dentate gyrus granule neurons via activation of the N-methyl-d-aspartate/extracellular signal-regulated kinase/mitogen- and stress-activated kinase signalling pathway. Eur J Neurosci 27:2701–2713PubMedGoogle Scholar
  176. 176.
    Renthal W, Nestler EJ (2008) Epigenetic mechanisms in drug addiction. Trends Mol Med 14:341–350PubMedGoogle Scholar
  177. 177.
    Xu WS, Parmigiani RB, Marks PA (2007) Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene 26:5541–5552PubMedGoogle Scholar
  178. 178.
    Dokmanovic M, Marks PA (2005) Prospects: histone deacetylase inhibitors. J Cell Biochem 96:293–304PubMedGoogle Scholar
  179. 179.
    Abel T, Zukin RS (2008) Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders. Curr Opin Pharmacol 8:57–64PubMedGoogle Scholar
  180. 180.
    Nestler EJ (2009) Epigenetic mechanisms in psychiatry. Biol Psychiatry 65:189–190PubMedGoogle Scholar
  181. 181.
    Kalsi G, Prescott CA, Kendler KS, Riley BP (2009) Unraveling the molecular mechanisms of alcohol dependence. Trends Genet 25:49–55PubMedGoogle Scholar
  182. 182.
    Ishii T, Hashimoto E, Ukai W, Tateno M, Yoshinaga T, Ono T, Watanabe K, Saito S, Saito T (2008) Epigenetic regulation in alcohol-related brain damage. Nihon Arukoru Yakubutsu Igakkai Zasshi 43:705–713PubMedGoogle Scholar
  183. 183.
    Kim JS, Shukla SD (2006) Acute in vivo effect of ethanol (binge drinking) on histone H3 modifications in rat tissues. Alcohol Alcohol 41:126–132PubMedGoogle Scholar
  184. 184.
    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 108:920–931PubMedGoogle Scholar
  185. 185.
    Wysocka J, Allis CD, Coonrod S (2006) Histone arginine methylation and its dynamic regulation. Front Biosci 11:344–355PubMedGoogle Scholar
  186. 186.
    Agger K, Christensen J, Cloos PA, Helin K (2008) The emerging functions of histone demethylases. Curr Opin Genet Dev 18:159–168PubMedGoogle Scholar
  187. 187.
    Cheung P, Lau P (2005) Epigenetic regulation by histone methylation and histone variants. Mol Endocrinol 19:563–573PubMedGoogle Scholar
  188. 188.
    Margueron R, Trojer P, Reinberg D (2005) The key to development: interpreting the histone code? Curr Opin Genet Dev 15:163–176PubMedGoogle Scholar
  189. 189.
    Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705PubMedGoogle Scholar
  190. 190.
    Okano M, Bell DW, Haber DA, Li E (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99:247–257PubMedGoogle Scholar
  191. 191.
    Bestor TH (2000) The DNA methyltransferases of mammals. Hum Mol Genet 9:2395–2402PubMedGoogle Scholar
  192. 192.
    Comb M, Goodman HM (1990) CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2. Nucleic Acids Res 18:3975–3982PubMedGoogle Scholar
  193. 193.
    Kalluri HS, Mehta AK, Ticku MK (1998) Up-regulation of NMDA receptor subunits in rat brain following chronic ethanol treatment. Brain Res Mol Brain Res 58:221–224PubMedGoogle Scholar
  194. 194.
    Marutha Ravindran CR, Ticku MK (2005) Role of CpG islands in the up-regulation of NMDA receptor NR2B gene expression following chronic ethanol treatment of cultured cortical neurons of mice. Neurochem Int 46:313–327PubMedGoogle Scholar
  195. 195.
    Bonsch D, Lenz B, Kornhuber J, Bleich S (2005) DNA hypermethylation of the alpha synuclein promoter in patients with alcoholism. Neuroreport 16:167–170PubMedGoogle Scholar
  196. 196.
    Pietrzykowski AZ, Friesen RM, Martin GE, Puig SI, Nowak CL, Wynne PM, Siegelmann HT, Treistman SN (2008) Posttranscriptional regulation of BK channel splice variant stability by miR-9 underlies neuroadaptation to alcohol. Neuron 59:274–287PubMedGoogle Scholar
  197. 197.
    Cowmeadow RB, Krishnan HR, Atkinson NS (2005) The slowpoke gene is necessary for rapid ethanol tolerance in Drosophila. Alcohol Clin Exp Res 29:1777–1786PubMedGoogle Scholar
  198. 198.
    Sathyan P, Golden HB, Miranda RC (2007) Competing interactions between micro-RNAs determine neural progenitor survival and proliferation after ethanol exposure: evidence from an ex vivo model of the fetal cerebral cortical neuroepithelium. J Neurosci 27:8546–8557PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  • Sachin Moonat
    • 1
    • 3
  • Bela G. Starkman
    • 1
    • 2
    • 3
  • Amul Sakharkar
    • 1
    • 3
  • Subhash C. Pandey
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Department of PsychiatryUniversity of Illinois at ChicagoChicagoUSA
  2. 2.Department of Anatomy and Cell BiologyUniversity of Illinois at ChicagoChicagoUSA
  3. 3.Jesse Brown VA Medical CenterChicagoUSA
  4. 4.Department of PsychiatryUniversity of Illinois at Chicago and Jesse Brown VA Medical CenterChicagoUSA

Personalised recommendations