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Cytosolic proteomic alterations in the nucleus accumbens of cocaine overdose victims

Molecular Psychiatry volume 12, pages 55–73 (2007)Cite this article

Abstract

Chronic cocaine use in humans and animal models is known to lead to pronounced alterations in neuronal function in the nucleus accumbens (NAc), a brain region associated with drug reinforcement. Two-dimensional gel electrophoresis was used to compare protein alterations in the NAc between cocaine overdose (COD) victims (n=10) and controls (n=10). Following image normalization, spots with significantly differential image intensities (P<0.05) were identified, excised, trypsin digested and analyzed by matrix-assisted laser desorption ionization-time of flight-time of flight. A total of 1407 spots were found to be present in a minimum of five subjects per group and the intensity of 18 spots was found to be differentially abundant between the groups, leading to positive identification of 15 proteins by peptide mass fingerprinting (PMF). Of an additional 37 protein spots that were constitutively expressed, 32 proteins were positively identified by PMF. Increased proteins in COD included β-tubulin, liprin-α3 and neuronal enolase, whereas decreased proteins included parvalbumin, ATP synthase β-chain and peroxiredoxin 2. The present data provide a preliminary protein profile of COD, suggesting the involvement of novel proteins and pathways in the expression of this complex disease. Additional studies are warranted to further characterize alterations in the differentially regulated proteins. Understanding the coordinated involvement of multiple proteins in cocaine abuse provides insight into the molecular basis of the disease and offers new targets for pharmacotherapeutic intervention for drug abuse-related disorders.

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References

  1. DSM-IV. Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association: Washington, DC, 1994.

  2. Wise RA, Bozarth MA . A psychomotor stimulant theory of addiction. Psychol Rev 1987; 94: 469–492.

    Article  CAS  PubMed  Google Scholar 

  3. Wise RA . Drug-activation of brain reward pathways. Drug Alcohol Depend 1998; 51: 13–22.

    Article  CAS  PubMed  Google Scholar 

  4. Koob GF, Sanna PP, Bloom FE . Neuroscience of addiction. Neuron 1998; 21: 467–476.

    Article  CAS  PubMed  Google Scholar 

  5. Koob GF, Nestler EJ . The neurobiology of drug addiction. J Neuropsychiatry Clin Neurosci 1997; 9: 482–497.

    Article  CAS  PubMed  Google Scholar 

  6. Breiter HC, Gollub RL, Weisskoff RM, Kennedy DN, Makris N, Berke JD et al. Acute effects of cocaine on human brain activity and emotion. Neuron 1997; 19: 591–611.

    Article  CAS  PubMed  Google Scholar 

  7. Kilts CD, Schweitzer JB, Quinn CK, Gross RE, Faber TL, Muhammad F et al. Neural activity related to drug craving in cocaine addiction. Arch Gen Psychiatry 2001; 58: 334–341.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  9. Hemby SE, Johnson BA, Dworkin SI . Neurobiological basis of drug reinforcement. In: Johnson BA, Roache JD (eds). Drug Addiction and Its Treatment: Nexus of Neuroscience and Behavior. Lippincott-Raven Publishers: Philadelphia, 1997, pp 137–169.

    Google Scholar 

  10. Hemby SE, Co C, Dworkin SI, Smith JE . Synergistic elevations in nucleus accumbens extracellular dopamine concentrations during self-administration of cocaine/heroin combinations (Speedball) in rats. J Pharmacol Exp Ther 1999; 288: 274–280.

    CAS  PubMed  Google Scholar 

  11. Hemby SE, Co C, Koves TR, Smith JE, Dworkin SI . Differences in extracellular dopamine concentrations in the nucleus accumbens during response-dependent and response-independent cocaine administration in the rat. Psychopharmacology (Berl) 1997; 133: 7–16.

    Article  CAS  Google Scholar 

  12. Pettit HO, Ettenberg A, Bloom FE, Koob GF . Destruction of dopamine in the nucleus accumbens selectively attenuates cocaine but not heroin self-administration in rats. Psychopharmacology 1984; 84: 167–173.

    Article  CAS  PubMed  Google Scholar 

  13. Pettit HO, Pan HT, Parsons LH, Justice Jr JB . Extracellular concentrations of cocaine and dopamine are enhanced during chronic cocaine administration. J Neurochem 1990; 55: 798–804.

    Article  CAS  PubMed  Google Scholar 

  14. Zito KA, Vickers G, Roberts DC . Disruption of cocaine and heroin self-administration following kainic acid lesions of the nucleus accumbens. Pharmacol Biochem Behav 1985; 23: 1029–1036.

    Article  CAS  PubMed  Google Scholar 

  15. White FJ, Kalivas PW . Neuroadaptations involved in amphetamine and cocaine addiction. Drug Alcohol Depend 1998; 51: 141–153.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  18. Nestler EJ, Aghajanian GK . Molecular and cellular basis of addiction. Science 1997; 278: 58–63.

    Article  CAS  PubMed  Google Scholar 

  19. Risinger RC, Salmeron BJ, Ross TJ, Amen SL, Sanfilipo M, Hoffmann RG et al. Neural correlates of high and craving during cocaine self-administration using BOLD fMRI. NeuroImage 2005; 26: 1097–1108.

    Article  PubMed  Google Scholar 

  20. Miserendino MJ, Nestler EJ . Behavioral sensitization to cocaine: modulation by the cyclic AMP system in the nucleus accumbens. Brain Res 1995; 674: 299–306.

    Article  CAS  PubMed  Google Scholar 

  21. Self DW, Genova LM, Hope BT, Barnhart WJ, Spencer JJ, Nestler EJ . Involvement of cAMP-dependent protein kinase in the nucleus accumbens in cocaine self-administration and relapse of cocaine-seeking behavior. J Neurosci 1998; 18: 1848–1859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Pliakas AM, Carlson RR, Neve RL, Konradi C, Nestler EJ, Carlezon Jr WA . Altered responsiveness to cocaine and increased immobility in the forced swim test associated with elevated cAMP response element-binding protein expression in nucleus accumbens. J Neurosci 2001; 21: 7397–7403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Carlezon Jr WA, Thome J, Olson VG, Lane-Ladd SB, Brodkin ES, Hiroi N et al. Regulation of cocaine reward by CREB. Science 1998; 282: 2272–2275.

    Article  CAS  PubMed  Google Scholar 

  24. Nestler EJ, Terwilliger RZ, Walker JR, Sevarino KA, Duman RS . Chronic cocaine treatment decreases levels of the G protein subunits Gi alpha and Go alpha in discrete regions of rat brain. J Neurochem 1990; 55: 1079–1082.

    Article  CAS  PubMed  Google Scholar 

  25. Striplin CD, Kalivas PW . Correlation between behavioral sensitization to cocaine and G protein ADP-ribosylation in the ventral tegmental area. Brain Res 1992; 579: 181–186.

    Article  CAS  PubMed  Google Scholar 

  26. Terwilliger RZ, Beitner-Johnson D, Sevarino KA, Crain SM, Nestler EJ . A general role for adaptations in G-proteins and the cyclic AMP system in mediating the chronic actions of morphine and cocaine on neuronal function. Brain Res 1991; 548: 100–110.

    Article  CAS  PubMed  Google Scholar 

  27. Hope B, Kosofsky B, Hyman SE, Nestler EJ . Regulation of immediate early gene expression and AP-1 binding in the rat nucleus accumbens by chronic cocaine. Proc Natl Acad Sci USA 1992; 89: 5764–5768.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Nye HE, Hope BT, Kelz MB, Iadarola M, Nestler EJ . Pharmacological studies of the regulation of chronic FOS-related antigen induction by cocaine in the striatum and nucleus accumbens. J PharmacolExp Ther 1995; 275: 1671–1680.

    CAS  Google Scholar 

  29. Pich EM, Pagliusi SR, Tessari M, Talabot-Ayer D, Hooft van Huijsduijnen R, Chiamulera C . Common neural substrates for the addictive properties of nicotine and cocaine. Science 1997; 275: 83–86.

    Article  CAS  PubMed  Google Scholar 

  30. Hiroi N, Brown JR, Haile CN, Ye H, Greenberg ME, Nestler EJ . 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 1997; 94: 10397–10402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Haile CN, Hiroi N, Nestler EJ, Kosten TA . Differential behavioral responses to cocaine are associated with dynamics of mesolimbic dopamine proteins in Lewis and Fischer 344 rats. Synapse 2001; 41: 179–190.

    Article  CAS  PubMed  Google Scholar 

  32. McClung CA, Nestler EJ . Regulation of gene expression and cocaine reward by CREB and DeltaFosB. Nat Neurosci 1208; 6: 1208–1215.

    Article  CAS  Google Scholar 

  33. Zhang D, Zhang L, Tang Y, Zhang Q, Lou D, Sharp FR et al. Repeated cocaine administration induces gene expression changes through the dopamine D1 receptors. Neuropsychopharmacology 2005; 30: 1443–1454.

    Article  CAS  PubMed  Google Scholar 

  34. Tang W, Wesley M, Freeman WM, Liang B, Hemby SE . Alterations in ionotropic glutamate receptor subunits during binge cocaine self-administration and withdrawal in rats. J Neurochem 2004; 89: 1021–1033.

    Article  CAS  PubMed  Google Scholar 

  35. Yuferov V, Nielsen D, Butelman E, Kreek MJ . Microarray studies of psychostimulant-induced changes in gene expression. Addict Biol 2005; 10: 101–118.

    Article  CAS  PubMed  Google Scholar 

  36. Yuferov V, Kroslak T, Laforge KS, Zhou Y, Ho A, Kreek MJ . Differential gene expression in the rat caudate putamen after ‘binge’ cocaine administration: advantage of triplicate microarray analysis. Synapse 2003; 48: 157–169.

    Article  CAS  PubMed  Google Scholar 

  37. Backes E, Hemby SE . Discrete cell gene profiling of ventral tegmental dopamine neurons after acute and chronic cocaine self-administration. J Pharmacol Exp Ther 2003; 307: 450–459.

    Article  CAS  PubMed  Google Scholar 

  38. Hemby SE, Horman B, Tang W . Differential regulation of ionotropic glutamate receptor subunits following cocaine self-administration. Brain Res 2005; 1064: 75–82.

    Article  CAS  PubMed  Google Scholar 

  39. Ang E, Chen J, Zagouras P, Magna H, Holland J, Schaeffer E et al. Induction of nuclear factor-kappaB in nucleus accumbens by chronic cocaine administration. J Neurochem 2001; 79: 221–224.

    Article  CAS  PubMed  Google Scholar 

  40. Yao WD, Gainetdinov RR, Arbuckle MI, Sotnikova TD, Cyr M, Beaulieu JM et al. Identification of PSD-95 as a regulator of dopamine-mediated synaptic and behavioral plasticity. Neuron 2004; 41: 625–638.

    Article  CAS  PubMed  Google Scholar 

  41. Bahi A, Dreyer JL . Cocaine-induced expression changes of axon guidance molecules in the adult rat brain. Mol Cell Neurosci 2005; 28: 275–291.

    Article  CAS  PubMed  Google Scholar 

  42. Albertson DN, Pruetz B, Schmidt CJ, Kuhn DM, Kapatos G, Bannon MJ . Gene expression profile of the nucleus accumbens of human cocaine abusers: evidence for dysregulation of myelin. J Neurochem 2004; 88: 1211–1219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Tang W-X, Fasulo WH, Mash DC, Hemby SE . Molecular profiling of midbrain dopamine regions in cocaine overdose victims. J Neurochem 2003; 85: 911–924.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hemby SE, Tang W, Muly EC, Kuhar MJ, Howell L, Mash DC . Cocaine-induced alterations in nucleus accumbens ionotropic glutamate receptor subunits in human and non-human primates. J Neurochem 2005; 95: 1785–1793.

    Article  CAS  PubMed  Google Scholar 

  45. Lehrmann E, Oyler J, Vawter MP, Hyde TM, Kolachana B, Kleinman JE et al. Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse. Pharmacogenomics J 2003; 3: 27–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Alexander-Kaufman K, James G, Sheedy D, Harper C, Matsumoto I . Differential protein expression in the prefrontal white matter of human alcoholics: a proteomics study. Mol Psychiatry 2006; 11: 56–65.

    Article  CAS  PubMed  Google Scholar 

  47. Freeman WM, Hemby SE . Proteomics for protein expression profiling in neuroscience. Neurochem Res 2004; 29: 1065–1081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Clark D, Dedova I, Cordwell S, & Matsumoto I . A proteome analysis of the anterior cingulate cortex gray matter in schizophrenia. Mol Psychiatry 2006; 11: 423, 459–470.

    Article  CAS  PubMed  Google Scholar 

  49. Prabakaran S, Swatton JE, Ryan MM, Huffaker SJ, Huang JT, Griffin JL et al. Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry 2004; 9: 684–697, 643.

    Article  CAS  PubMed  Google Scholar 

  50. Swatton JE, Prabakaran S, Karp NA, Lilley KS, Bahn S . Protein profiling of human postmortem brain using 2-dimensional fluorescence difference gel electrophoresis (2-D DIGE). Mol Psychiatry 2004; 9: 128–143.

    Article  CAS  PubMed  Google Scholar 

  51. Johnston-Wilson NL, Sims CD, Hofmann JP, Anderson L, Shore AD, Torrey EF et al. Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. The Stanley Neuropathology Consortium. Mol Psychiatry 2000; 5: 142–149.

    Article  CAS  PubMed  Google Scholar 

  52. Gorg A, Obermaier C, Boguth G, Harder A, Scheibe B, Wildgruber R et al. The current state of two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis 2000; 21: 1037–1053.

    Article  CAS  PubMed  Google Scholar 

  53. Tonge R, Shaw J, Middleton B, Rowlinson R, Rayner S, Young J et al. Validation and development of fluorescence two-dimensional differential gel electrophoresis proteomics technology. Proteomics 2001; 1: 377–396.

    Article  CAS  PubMed  Google Scholar 

  54. Unlu M, Morgan ME, Minden JS . Difference gel electrophoresis: a single gel method for detecting changes in protein extracts. Electrophoresis 1997; 18: 2071–2077.

    Article  CAS  PubMed  Google Scholar 

  55. Dhingra V, Li Q, Allison AB, Stallknecht DE, Fu ZF . Proteomic profiling and neurodegeneration in west-nile-virus-infected neurons. J Biomed Biotechnol 2005; 2005: 271–279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Bruggeman V, Van den Bergh G, Clerens S, Dumez L, Onagbesan O, Arckens L et al. Effect of a single in ovo injection of 2,3,7,8-tetrachlorodibenzo-p-dioxin on protein expression in liver and ovary of the one-day-old chick analyzed by fluorescent two-dimensional difference gel electrophoresis and mass spectrometry. Proteomics 2006; 6: 2576–2585.

    Article  CAS  PubMed  Google Scholar 

  57. Henzel WJ, Billeci TM, Stults JT, Wong SC, Grimley C, Watanabe C . Identifying proteins from two-dimensional gels by molecular mass searching of peptide fragments in protein sequence databases. Proc Natl Acad Sci USA 1993; 90: 5011–5015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Mann M, Hojrup P, Roepstorff P . Use of mass spectrometric molecular weight information to identify proteins in sequence databases. Biol Mass Spectrom 1993; 22: 338–345.

    Article  CAS  PubMed  Google Scholar 

  59. Pappin DJ . Peptide mass fingerprinting using MALDI-TOF mass spectrometry. Methods Mol Biol 2003; 211: 211–219.

    CAS  PubMed  Google Scholar 

  60. Stephens BG, Jentzen JM, Karch S, Mash DC, Wetli CV . Criteria for the interpretation of cocaine levels in human biological samples and their relation to the cause of death. Am J Forensic Med Pathol 2004; 25: 1–10.

    Article  PubMed  Google Scholar 

  61. Stephens BG, Jentzen JM, Karch S, Wetli CV, Mash DC . National Association of Medical Examiners position paper on the certification of cocaine-related deaths. Am J Forensic Med Pathol 2004; 25: 11–13.

    Article  PubMed  Google Scholar 

  62. Hernandez A, Andollo W, Hearn WL . Analysis of cocaine and metabolites in brain using solid phase extraction and full-scanning gas chromatography/ion trap mass spectrometry. Forensic Sci Int 1994; 65: 149–156.

    Article  CAS  PubMed  Google Scholar 

  63. Alban A, David SO, Bjorkesten L, Andersson C, Sloge E, Lewis S et al. A novel experimental design for comparative two-dimensional gel analysis: two-dimensional difference gel electrophoresis incorporating a pooled internal standard. Proteomics 2003; 3: 36–44.

    Article  CAS  PubMed  Google Scholar 

  64. Berggren KN, Chernokalskaya E, Lopez MF, Beechem JM, Patton WF . Comparison of three different fluorescent visualization strategies for detecting Escherichia coli ATP synthase subunits after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Proteomics 2001; 1: 54–65.

    Article  CAS  PubMed  Google Scholar 

  65. Bjellqvist B, Ek K, Righetti PG, Gianazza E, Gorg A, Westermeier R et al. Isoelectric focusing in immobilized pH gradients: principle, methodology and some applications. J Biochem Biophys Methods 1982; 6: 317–339.

    Article  CAS  PubMed  Google Scholar 

  66. Tannu NS, Wu J, Rao VK, Gadgil HS, Pabst MJ, Gerling IC et al. Paraffin-wax-coated plates as matrix-assisted laser desorption/ionization sample support for high-throughput identification of proteins by peptide mass fingerprinting. Anal Biochem 2004; 327: 222–232.

    Article  CAS  PubMed  Google Scholar 

  67. O’Farrell PH . High resolution two-dimensional electrophoresis of proteins. J Biol Chem 1975; 250: 4007–4021.

    PubMed  Google Scholar 

  68. Weber K, Osborn M . The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem 1969; 244: 4406–4412.

    CAS  PubMed  Google Scholar 

  69. Tannu NS, Sanchez-Brambila G, Kirby P, Andacht TM . Effect of staining reagent on peptide mass fingerprinting from in-gel trypsin digestions: a comparison of SyproRuby™ and DeepPurple™. Electrophoresis 2006; 27: 3136–3143.

    Article  CAS  PubMed  Google Scholar 

  70. Patterson SD, Aebersold R . Mass spectrometric approaches for the identification of gel-separated proteins. Electrophoresis 1995; 16: 1791–1814.

    Article  CAS  PubMed  Google Scholar 

  71. Gharahdaghi F, Weinberg CR, Meagher DA, Imai BS, Mische SM . Mass spectrometric identification of proteins from silver-stained polyacrylamide gel: a method for the removal of silver ions to enhance sensitivity. Electrophoresis 1999; 20: 601–605.

    Article  CAS  PubMed  Google Scholar 

  72. Tannu NS, Rao VK, Chaudhary RM, Giorgianni F, Saeed AE, Gao Y et al. Comparative proteomes of the proliferating C(2)C(12) myoblasts and fully differentiated myotubes reveal the complexity of the skeletal muscle differentiation program. Mol Cell Proteomics 2004; 3: 1065–1082.

    Article  CAS  PubMed  Google Scholar 

  73. Mann M, Wilm M . Error-tolerant identification of peptides in sequence databases by peptide sequence tags. Anal Chem 1994; 66: 4390–4399.

    Article  CAS  PubMed  Google Scholar 

  74. Yates III JR . Database searching using mass spectrometry data. Electrophoresis 1998; 19: 893–900.

    Article  CAS  PubMed  Google Scholar 

  75. Pappin DJ, Hojrup P, Bleasby AJ . Rapid identification of proteins by peptide-mass fingerprinting. Curr Biol 1993; 3: 327–332.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  77. Sutton MA, Schmidt EF, Choi KH, Schad CA, Whisler K, Simmons D et al. Extinction-induced upregulation in AMPA receptors reduces cocaine-seeking behaviour. Nature 2003; 421: 70–75.

    Article  CAS  PubMed  Google Scholar 

  78. Lu L, Grimm JW, Shaham Y, Hope BT . Molecular neuroadaptations in the accumbens and ventral tegmental area during the first 90 days of forced abstinence from cocaine self-administration in rats. J Neurochem 2003; 85: 1604–1613.

    Article  CAS  PubMed  Google Scholar 

  79. Nestler EJ . Cellular responses to chronic treatment with drugs of abuse. Crit Rev Neurobiol 1993; 7: 23–39.

    CAS  PubMed  Google Scholar 

  80. Wyszynski M, Kim E, Dunah AW, Passafaro M, Valtschanoff JG, Serra-Pages C et al. Interaction between GRIP and liprin-alpha/SYD2 is required for AMPA receptor targeting. Neuron 2002; 34: 39–52.

    Article  CAS  PubMed  Google Scholar 

  81. Shin H, Wyszynski M, Huh KH, Valtschanoff JG, Lee JR, Ko J et al. Association of the kinesin motor KIF1A with the multimodular protein liprin-alpha. J Biol Chem 2003; 278: 11393–11401.

    Article  CAS  PubMed  Google Scholar 

  82. Serra-Pages C, Medley QG, Tang M, Hart A, Streuli M . Liprins, a family of LAR transmembrane protein-tyrosine phosphatase-interacting proteins. J Biol Chem 1998; 273: 15611–15620.

    Article  CAS  PubMed  Google Scholar 

  83. Hata Y, Butz S, Sudhof TC . CASK: a novel dlg/PSD95 homolog with an N-terminal calmodulin-dependent protein kinase domain identified by interaction with neurexins. J Neurosci 1996; 16: 2488–2494.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Okamoto M, Sudhof TC . Mints, Munc18-interacting proteins in synaptic vesicle exocytosis. J Biol Chem 1997; 272: 31459–31464.

    Article  CAS  PubMed  Google Scholar 

  85. Jo K, Derin R, Li M, Bredt DS . Characterization of MALS/Velis-1, -2, and -3: a family of mammalian LIN-7 homologs enriched at brain synapses in association with the postsynaptic density-95/NMDA receptor postsynaptic complex. J Neurosci 1999; 19: 4189–4199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Setou M, Nakagawa T, Seog DH, Hirokawa N . Kinesin superfamily motor protein KIF17 and mLin-10 in NMDA receptor-containing vesicle transport. Science 2000; 288: 1796–1802.

    Article  CAS  PubMed  Google Scholar 

  87. Cornish JL, Kalivas PW . Glutamate transmission in the nucleus accumbens mediates relapse in cocaine addiction. J Neurosci 2000; 20: RC89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Park WK, Bari AA, Jey AR, Anderson SM, Spealman RD, Rowlett JK et al. Cocaine administered into the medial prefrontal cortex reinstates cocaine-seeking behavior by increasing AMPA receptor-mediated glutamate transmission in the nucleus accumbens. J Neurosci 2002; 22: 2916–2925.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Lu W, Monteggia LM, Wolf ME . Repeated administration of amphetamine and cocaine does not alter AMPA receptor subunit expression in the rat midbrain. Neuropsychopharmacology 2002; 26: 1–13.

    Article  PubMed  Google Scholar 

  90. Porrino LJ . Functional consequences of acute cocaine treatment depend on route of administration. Psychopharmacology (Berl) 1993; 112: 343–351.

    Article  CAS  Google Scholar 

  91. Lyons D, Friedman DP, Nader MA, Porrino LJ . Cocaine alters cerebral metabolism within the ventral striatum and limbic cortex of monkeys. J Neurosci 1996; 16: 1230–1238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Porrino LJ, Lyons D, Smith HR, Daunais JB, Nader MA . Cocaine self-administration produces a progressive involvement of limbic, association, and sensorimotor striatal domains. J Neurosci 2004; 24: 3554–3562.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Rhee SG, Chae HZ, Kim K . Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling. Free Radic Biol Med 2005; 38: 1543–1552.

    Article  CAS  PubMed  Google Scholar 

  94. Sarafian TA, Verity MA, Vinters HV, Shih CC, Shi L, Ji XD et al. Differential expression of peroxiredoxin subtypes in human brain cell types. J Neurosci Res 1999; 56: 206–212.

    Article  CAS  PubMed  Google Scholar 

  95. Yim MB, Chae HZ, Rhee SG, Chock PB, Stadtman ER . On the protective mechanism of the thiol-specific antioxidant enzyme against the oxidative damage of biomacromolecules. J Biol Chem 1994; 269: 1621–1626.

    CAS  PubMed  Google Scholar 

  96. Netto LES, Chae HZ, Kang SW, Rhee SG, Stadtman ER . Removal of hydrogen peroxide by thiol-specific antioxidant enzyme (TSA) is involved with its antioxidant properties. TSA possesses thiol peroxidase activity. J Biol Chem 1996; 271: 15315–15321.

    Article  CAS  Google Scholar 

  97. Kim H, Lee TH, Park ES, Suh JM, Park SJ, Chung HK et al. Role of peroxiredoxins in regulating intracellular hydrogen peroxide and hydrogen peroxide-induced apoptosis in thyroid cells. J Biol Chem 2000; 275: 18266–18270.

    Article  CAS  PubMed  Google Scholar 

  98. Kloss MW, Rosen GM, Rauckman EJ . Biotransformation of norcocaine to norcocaine nitroxide by rat brain microsomes. Psychopharmacology (Berl) 1984; 84: 221–224.

    Article  CAS  Google Scholar 

  99. Dietrich JB, Mangeol A, Revel MO, Burgun C, Aunis D, Zwiller J . Acute or repeated cocaine administration generates reactive oxygen species and induces antioxidant enzyme activity in dopaminergic rat brain structures. Neuropharmacology 2005; 48: 965–974.

    Article  CAS  PubMed  Google Scholar 

  100. Macedo DS, de Vasconcelos SM, dos Santos RS, Aguiar LM, Lima VT, Viana GS et al. Cocaine alters catalase activity in prefrontal cortex and striatum of mice. Neurosci Lett 2005; 387: 53–56.

    Article  CAS  PubMed  Google Scholar 

  101. Dietrich JB, Poirier R, Aunis D, Zwiller J . Cocaine downregulates the expression of the mitochondrial genome in rat brain. Ann NY Acad Sci 2004; 1025: 345–350.

    Article  CAS  PubMed  Google Scholar 

  102. Zhang XF, Cooper DC, White FJ . Repeated cocaine treatment decreases whole-cell calcium current in rat nucleus accumbens neurons. J Pharmacol Exp Ther 2002; 301: 1119–1125.

    Article  CAS  PubMed  Google Scholar 

  103. Howe CL, Mobley WC . Signaling endosome hypothesis: a cellular mechanism for long distance communication. J Neurobiol 2004; 58: 207–216.

    Article  PubMed  Google Scholar 

  104. Collins MO, Yu L, Coba MP, Husi H, Campuzano I, Blackstock WP et al. Proteomic analysis of in vivo phosphorylated synaptic proteins. J Biol Chem 2005; 280: 5972–5982.

    Article  CAS  PubMed  Google Scholar 

  105. Goldstein LS . Do disorders of movement cause movement disorders and dementia? Neuron 2003; 40: 415–425.

    Article  CAS  PubMed  Google Scholar 

  106. Schlicht K, Buttner A, Siedler F, Scheffer B, Zill P, Eisenmenger W et al. Comparative proteomic analysis with postmortem prefrontal cortex tissues of suicide victims versus controls. J Psychiatr Res 2006, in press.

  107. Korolainen MA, Auriola S, Nyman TA, Alafuzoff I, Pirttila T . Proteomic analysis of glial fibrillary acidic protein in Alzheimer's disease and aging brain. Neurobiol Dis 2005; 20: 858–870.

    Article  CAS  PubMed  Google Scholar 

  108. Tsuji T, Shimohama S . Analysis of the proteomic profiling of brain tissue in Alzheimer's disease. Dis Markers 2001; 17: 247–257.

    Article  CAS  PubMed  Google Scholar 

  109. Yang JW, Czech T, Gelpi E, Lubec G . Extravasation of plasma proteins can confound interpretation of proteomic studies of brain: a lesson from apo A-I in mesial temporal lobe epilepsy. Brain Res Mol Brain Res 2005; 139: 348–356.

    Article  CAS  PubMed  Google Scholar 

  110. Haydon PG . GLIA: listening and talking to the synapse. Nat Rev Neurosci 2001; 2: 185–193.

    Article  CAS  PubMed  Google Scholar 

  111. Weinstein DE, Shelanski ML, Liem RK . Suppression by antisense mRNA demonstrates a requirement for the glial fibrillary acidic protein in the formation of stable astrocytic processes in response to neurons. J Cell Biol 1991; 112: 1205–1213.

    Article  CAS  PubMed  Google Scholar 

  112. Heizmann CW . Calcium-binding proteins: basic concepts and clinical implications. Gen Physiol Biophys 1992; 11: 411–425.

    CAS  PubMed  Google Scholar 

  113. Koos T, Tepper JM . Inhibitory control of neostriatal projection neurons by GABAergic interneurons. Nat Neurosci 1999; 2: 467–472.

    Article  CAS  PubMed  Google Scholar 

  114. Zahm DS, Grosu S, Irving JC, Williams EA . Discrimination of striatopallidum and extended amygdala in the rat: a role for parvalbumin immunoreactive neurons? Brain Res 2003; 978: 141–154.

    Article  CAS  PubMed  Google Scholar 

  115. Todtenkopf MS, Stellar JR, Williams EA, Zahm DS . Differential distribution of parvalbumin immunoreactive neurons in the striatum of cocaine sensitized rats. Neuroscience 2004; 127: 35–42.

    Article  CAS  PubMed  Google Scholar 

  116. Zhu JP, Xu W, Angulo JA . Methamphetamine-induced cell death: selective vulnerability in neuronal subpopulations of the striatum in mice. Neuroscience 2006; 140: 607–622.

    Article  CAS  PubMed  Google Scholar 

  117. Tannu N, Hemby SE . Methods for proteomics in neuroscience. In: Hemby SE, Bahn S (eds). Progress in Brain Research: Functional Genomics and Proteomics in the Clinical Neurosciences. Elsevier: Amsterdam, in press.

  118. Knowles MR, Cervino S, Skynner HA, Hunt SP, de Felipe C, Salim K et al. Multiplex proteomic analysis by two-dimensional differential in-gel electrophoresis. Proteomics 2003; 3: 1162–1171.

    Article  CAS  PubMed  Google Scholar 

  119. Shaw J, Knowles MR, Cervino S, Skynner HA, Hunt SP, de Felipe C et al. Evaluation of saturation labelling two-dimensional difference gel electrophoresis fluorescent dyes. Proteomics 2003; 3: 1181–1195.

    Article  CAS  PubMed  Google Scholar 

  120. Hemby SE . Assessment of genome and proteome profiles in cocaine abuse. In: Hemby SE, Bahn S (eds). Progress in Brian Research: Functional Genomics and Proteomics in the Clinical Neurosciences. Elsevier: New York, in press.

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Acknowledgements

This research was supported by National Institutes of Health Grant R01DA013772.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    N Tannu & S E Hemby

  2. Department of Neurology, University of Miami School of Medicine, Miami, FL, USA

    D C Mash

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  1. N Tannu
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  2. D C Mash
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  3. S E Hemby
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Correspondence to S E Hemby.

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Tannu, N., Mash, D. & Hemby, S. Cytosolic proteomic alterations in the nucleus accumbens of cocaine overdose victims. Mol Psychiatry 12, 55–73 (2007). https://doi.org/10.1038/sj.mp.4001914

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  • DOI: https://doi.org/10.1038/sj.mp.4001914

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