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Transcriptional Mechanisms of Drug Addiction

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Regulation of gene expression is considered a plausible mechanism of drug addiction given the stability of behavioral abnormalities that define an addicted state. Numerous transcription factors, proteins that bind to regulatory regions of specific genes and thereby control levels of their expression, have been implicated in the addiction process over the past decade or two. Here we review the growing evidence for the role played by several prominent transcription factors, including a Fos family protein (ΔFosB), cAMP response element binding protein (CREB), and nuclear factor kappa B (NFκB), among several others,in drug addiction. As will be seen, each factor displays very different regulation by drugs of abuse within the brain's reward circuitry, and in turn mediates distinct aspects of the addiction phenotype. Current efforts are geared toward understanding the range of target genes through which these transcription factors produce their functional effects and the underlying molecular mechanisms involved. This work promises to reveal fundamentally new insight into the molecular basis of addiction, which will contribute to improved diagnostic tests and therapeutics for addictive disorders.

Abstract

Regulation of gene expression is considered a plausible mechanism of drug addiction given the stability of behavioral abnormalities that define an addicted state. Numerous transcription factors, proteins that bind to regulatory regions of specific genes and thereby control levels of their expression, have been implicated in the addiction process over the past decade or two. Here we review the growing evidence for the role played by several prominent transcription factors, including a Fos family protein (ΔFosB), cAMP response element binding protein (CREB), and nuclear factor kappa B (NFκB), among several others,in drug addiction. As will be seen, each factor displays very different regulation by drugs of abuse within the brain's reward circuitry, and in turn mediates distinct aspects of the addiction phenotype. Current efforts are geared toward understanding the range of target genes through which these transcription factors produce their functional effects and the underlying molecular mechanisms involved. This work promises to reveal fundamentally new insight into the molecular basis of addiction, which will contribute to improved diagnostic tests and therapeutics for addictive disorders.

참고문헌 (55)

  1. Nestler EJ., "Molecular basis of long-term plasticity underlying addiction", Nat Rev Neurosci, 2, pp.119~128 (2001)
  2. Nestler EJ., "Transcriptional mechanisms of addiction: role of delta FosB", Philos Trans R Soc Lond B Biol Sci, 363, pp.3245~3255 (2008)
  3. Nestler EJ, "Molecular neurobiology of addiction", Am J Addict, 10, pp.201~217 (2001)
  4. Robison AJ, "Transcriptional and epigenetic mechanisms of addiction", Nat Rev Neurosci, 12, pp.623~637 (2011)
  5. Morgan JI, "Immediate-early genes: ten years on", Trends Neurosci, 18, pp.66~67 (1995)
  6. Perrotti LI, "Distinct patterns of DeltaFosB induction in brain by drugs of abuse", Synapse, 62, pp.358~369 (2008)
  7. Chen J, "Chronic Fos-related antigens: stable variants of deltaFosB induced in brain by chronic treatments", J Neurosci, 17, pp.4933~4941 (1997)
  8. Hiroi N, "FosB mutant mice: loss of chronic cocaine induction of Fos-related proteins and heightened sensitivity to cocaine's psychomotor and rewarding effects", Proc Natl Acad Sci USA, 94, pp.10397~10402 (1997)
  9. Renthal W, "Delta FosB mediates epigenetic desensitization of the c-fos gene after chronic amphetamine exposure", J Neurosci, 28, pp.7344~7349 (2008)
  10. Hiroi N, "Essential role of the fosB gene in molecular, cellular, and behavioral actions of chronic electroconvulsive seizures", J Neurosci, 18, pp.6952~6962 (1998)
  11. Jorissen H, "Dimerization and DNA-binding properties of the transcription factor DeltaFosB", Biochemistry, 46, pp.8360~8372 (2007)
  12. Winstanley CA, "DeltaFosB induction in orbitofrontal cortex mediates tolerance to cocaine-induced cognitive dysfunction", J Neurosci, 27, pp.10497~10507 (2007)
  13. Alibhai IN, "Regulation of fosB and DeltafosB mRNA expression: in vivo and in vitro studies", Brain Res, 1143, pp.22~33 (2007)
  14. Ulery PG, "Regulation of DeltaFosB stability by phosphorylation", J Neurosci, 26, pp.5131~5142 (2006)
  15. Ulery-Reynolds PG, "Phosphorylation of DeltaFosB mediates its stability in vivo", Neuroscience, 158, pp.369~372 (2009)
  16. Carle TL, "Absence of conserved C-terminal degron domain contributes to ΔFosB’s unique stability", Eur J Neurosci, 25, pp.3009~3019 (2007)
  17. Kelz MB, "Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine", Nat, 401, pp.272~276 (1999)
  18. McClung CA, "Regulation of gene expression and cocaine reward by CREB and DeltaFosB", Nat Neurosci, 6, pp.1208~1215 (2003)
  19. Zachariou V, "DeltaFosB: An essential role for DeltaFosB in the nucleus accumbens in morphine action", Nat Neurosci, 9, pp.205~211 (2006)
  20. Colby CR, "Striatal cell type-specific overexpression of DeltaFosB enhances incentive for cocaine", J Neurosci, 23, pp.2488~2493 (2003)
  21. Peakman MC, "Inducible, brain region specific expression of a dominant negative mutant of c-Jun in transgenic mice decreases sensitivity to cocaine", Brain Res, 970, pp.73~86 (2003)
  22. Winstanley CA, "Increased impulsivity during withdrawal from cocaine self-administration: role for DeltaFosB in the orbitofrontal cortex", Cereb Cortex, 19, pp.435~444 (2009)
  23. Kauer JA, "Synaptic plasticity and addiction", Nat Rev Neurosci, 8, pp.844~858 (2007)
  24. Shippenberg TS, "Sensitization to the behavioral effects of cocaine: modulation by dynorphin and kappaopioid receptor agonists", Pharmacol Biochem Behav, 57, pp.449~455 (1997)
  25. Bruchas MR, "The dynorphin", kappa opioid system as a modulator of stress-induced and proaddictive behaviors, 2010, pp.1314, 44~55
  26. Bibb JA, "Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5", Nature, 410, pp.376~380 (2001)
  27. Norrholm SD, "Cocaine-induced proliferation of dendritic spines in nucleus accumbens is dependent on the activity of cyclin-dependent kinase-5", Neuroscience, 116, pp.19~22 (2003)
  28. Pulipparacharuvil S, "Cocaine regulates MEF2 to control synaptic and behavioral plasticity", Neuron, 59, pp.621~633 (2008)
  29. Robinson TE, "Structural plasticity associated with exposure to drugs of abuse", Neuropharmacology, 47(Suppl 1), pp.33~46 (2004)
  30. Russo SJ, "The addicted synapse: mechanisms of synaptic and structural plasticity in nucleus accumbens", Trends Neurosci, 33, pp.267~276 (2010)
  31. Maze I, "Essential role of the histone methyltransferase G9a in cocaine-induced plasticity", Science, 327, pp.213~216 (2010)
  32. Renthal W, "Genome-wide analysis of chromatinregulation by cocaine reveals a role for sirtuins", Neuron, 62, pp.335~348 (2009)
  33. Mayr B, "Transcriptional regulation by the phosphorylation-dependent factor CREB", Nat Rev Mol Cell Biol, 2, pp.599~609 (2001)
  34. Carlezon WA Jr, "The many faces of CREB", Trends Neurosci, 28, pp.436~445 (2005)
  35. Graham DL, "Dynamic BDNF activity in nucleus accumbens with cocaine use increases self-administration and relapse", Nat Neurosci, 10, pp.1029~1037 (2007)
  36. Briand LA, "Molecular and genetic substrates linking stress and addiction", Brain Res, 1314, pp.219~234 (2010)
  37. Carlezon WA Jr, "Regulation of cocaine reward by CREB", Science, 282, pp.2272~2275 (1998)
  38. Barrot M, "CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli", Proc Natl Acad Sci U S A, 99, pp.11435~11440 (2002)
  39. Larson EB, "Overexpression of CREB in the nucleus accumbens shell increases cocaine reinforcement in selfadministering rats", J Neurosci, 31, pp.16447~16457 (2011)
  40. Green TA, "Environmental enrichment produces a behavioral phenotype mediated by low cyclic adenosine monophosphate response element binding (CREB) activity in the nucleus accumbens", Biol Psychiatry, 67, pp.28~35 (2010)
  41. Vialou V, "Serum response factor and cAMP response element binding protein are both required for cocaine induction of deltaFosB", J Neurosci, 32, pp.7577~7584 (2012)
  42. Dinieri JA, "Altered sensitivity to rewarding and aversive drugs in mice with inducible disruption of cAMP response element-binding protein function within the nucleus accumbens", J Neurosci, 29, pp.1855~1859 (2009)
  43. Dong Y, "CREB modulates excitability of nucleus accumbens neurons", Nat Neurosci, 9, pp.475~477 (2006)
  44. Huang YH, "CREB modulates the functional output of nucleus accumbens neurons: a critical role of N-methyl-D-aspartate glutamate receptor (NMDAR) receptors", J Biol Chem, 283, pp.2751~2760 (2008)
  45. Brown TE, "A silent synapse-based mechanism for cocaine-induced locomotor sensitization", J Neurosci, 31, pp.8163~8174 (2011)
  46. Green TA, "Induction of inducible cAMP early repressor expression in nucleus accumbens by stress or amphetamine increases behavioral responses to emotional stimuli", J Neurosci, 26, pp.8235~8242 (2006)
  47. Green TA, "Induction of activating transcription factors (ATFs) ATF2, ATF3, and ATF4 in the nucleus accumbens and their regulation of emotional behavior", J Neurosci, 28, pp.2025~2032 (2008)
  48. Meffert MK, "Physiological functions for brain NF-kappaB", Trends Neurosci, 28, pp.37~43 (2005)
  49. Ang E, "Induction of nuclear factor-kappaB in nucleus accumbens by chronic cocaine administration", J Neurochem, 79, pp.221~224 (2001)
  50. Russo SJ, "Nuclear factor kappa B signaling regulates neuronal morphology and cocaine reward", J Neurosci, 29, pp.3529~3537 (2009)
  51. Asanuma M, "Methamphetamine-induced increase in striatal NF-kappaB DNA-binding activity is attenuated in superoxide dismutase transgenic mice", Brain Res Mol Brain Res, 60, pp.305~309 (1998)
  52. Christoffel DJ, "IκB kinase regulates social defeat stress-induced synaptic and behavioral plasticity", J Neurosci, 31, pp.314~321 (2011)
  53. Flavell SW, "Genome-wide analysis of MEF2 transcriptional program reveals synaptic target genes and neuronal activity-dependent polyadenylation site selection", Neuron, 60, pp.1022~1038 (2008)
  54. Ambroggi F, "Stress and addiction: glucocorticoid receptor in dopaminoceptive neurons facilitates cocaine seeking", Nat Neurosci, 12, pp.247~249 (2009)
  55. Kumar A, "Chromatin remodeling is a key mechanism underlying cocaineinduced plasticity in striatum", Neuron, 48, pp.303~314 (2005)

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