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Journal of Neural Transmission

, Volume 122, Issue 10, pp 1391–1398 | Cite as

mRNA expression of dopamine receptors in peripheral blood lymphocytes of computer game addicts

  • Nasim VousooghiEmail author
  • Seyed Zeinolabedin Zarei
  • Mitra-Sadat Sadat-Shirazi
  • Fatemeh Eghbali
  • Mohammad Reza Zarrindast
Translational Neurosciences - Original Article

Abstract

Excessive playing of computer games like some other behaviors could lead to addiction. Addictive behaviors may induce their reinforcing effects through stimulation of the brain dopaminergic mesolimbic pathway. The status of dopamine receptors in the brain may be parallel to their homologous receptors in peripheral blood lymphocytes (PBLs). Here, we have investigated the mRNA expression of dopamine D3, D4 and D5 receptors in PBLs of computer game addicts (n = 20) in comparison to normal subjects (n = 20), using a real-time PCR method. The results showed that the expression level of D3 and D4 dopamine receptors in computer game addicts were not statistically different from the control group. However, the expression of the mRNA of D5 dopamine receptor was significantly down-regulated in PBLs of computer game addicts and reached 0.42 the amount of the control group. It is concluded that unlike with drug addiction, the expression levels of the D3 and D4 dopamine receptors in computer game addicts are not altered compared to the control group. However, reduced level of the D5 dopamine receptor in computer game addicts may serve as a peripheral marker in studies where the confounding effects of abused drugs are unwanted.

Keywords

Computer game addiction Lymphocyte Dopamine receptor mRNA expression 

Notes

Acknowledgments

The authors acknowledge the grant support of the Tehran University of Medical Sciences (91-03-49-19464).

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Barbanti P et al (2000) Reduced density of dopamine D2-like receptors on peripheral blood lymphocytes in Alzheimer’s disease. Mech Ageing Dev 120:65–75CrossRefPubMedGoogle Scholar
  2. Beninger RJ, Miller R (1998) Dopamine D1-like receptors and reward-related incentive learning. Neurosci Biobehav Rev 22:335–345CrossRefPubMedGoogle Scholar
  3. Boileau I et al (2012) Higher binding of the dopamine D3 receptor-preferring ligand [11C]-(+)-propyl-hexahydro-naphtho-oxazin in methamphetamine polydrug users: a positron emission tomography study. J Neurosci 32:1353–1359PubMedCentralCrossRefPubMedGoogle Scholar
  4. Boileau I et al (2013) The D2/3 dopamine receptor in pathological gambling: a positron emission tomography study with [11C]-(+)-propyl-hexahydro-naphtho-oxazin and [11C]raclopride. Addiction 108:953–963CrossRefPubMedGoogle Scholar
  5. Bondy B, Ackenheil M, Elbers R, Frohler M (1985) Binding of 3H-spiperone to human lymphocytes: a biological marker in schizophrenia? Psychiatry Res 15:41–48CrossRefPubMedGoogle Scholar
  6. Breiter HC, Aharon I, Kahneman D, Dale A, Shizgal P (2001) Functional imaging of neural responses to expectancy and experience of monetary gains and losses. Neuron 30:619–639CrossRefPubMedGoogle Scholar
  7. Carlsson A, Waters N, Carlsson ML (1999) Neurotransmitter interactions in schizophrenia-therapeutic implications. Eur Arch Psychiatry Clin Neurosci 249(Suppl 4):37–43CrossRefPubMedGoogle Scholar
  8. Ciliax BJ, Nash N, Heilman C, Sunahara R, Hartney A, Tiberi M, Rye DB, Caron MG, Niznik HB, Levey AI (2000) Dopamine D(5) receptor immunolocalization in rat and monkey brain. Synapse 37:125–145CrossRefPubMedGoogle Scholar
  9. Cole DM et al (2012) Orbitofrontal connectivity with resting-state networks is associated with midbrain dopamine D3 receptor availability. Cereb Cortex 22:2784–2793CrossRefPubMedGoogle Scholar
  10. Czermak C et al (2004a) Reduced dopamine D3 receptor expression in blood lymphocytes of smokers is negatively correlated with daily number of smoked cigarettes: a peripheral correlate of dopaminergic alterations in smokers. Nicotine Tob Res 6:49–54CrossRefPubMedGoogle Scholar
  11. Czermak C et al (2004b) Reduced dopamine D4 receptor mRNA expression in lymphocytes of long-term abstinent alcohol and heroin addicts. Addiction 99:251–257CrossRefPubMedGoogle Scholar
  12. Czlonkowska A, Jachowicz-Jeszka J, Czlonkowski A (1987) [3H]spiperone binding to lymphocyte in extrapyramidal disease and in aging. Brain Behav Immun 1:197–203CrossRefPubMedGoogle Scholar
  13. Czlonkowski A, Czlonkowska A (1984) Reduced binding of 3H-spiroperidol to lymphocyte in Wilson’s disease. Acta Neurol Scand 69:298–301CrossRefPubMedGoogle Scholar
  14. Di Chiara G (1995) The role of dopamine in drug abuse viewed from the perspective of its role in motivation. Drug Alcohol Depend 38:95–137CrossRefPubMedGoogle Scholar
  15. Di Chiara G, Tanda G, Cadoni C, Acquas E, Bassareo V, Carboni E (1998) Homologies and differences in the action of drugs of abuse and a conventional reinforcer (food) on dopamine transmission: an interpretative framework of the mechanism of drug dependence. Adv Pharmacol 42:983–987CrossRefPubMedGoogle Scholar
  16. Ding YC et al (2002) Evidence of positive selection acting at the human dopamine receptor D4 gene locus. Proc Natl Acad Sci USA 99:309–314PubMedCentralCrossRefPubMedGoogle Scholar
  17. Eisenegger C, Knoch D, Ebstein RP, Gianotti LR, Sandor PS, Fehr E (2010) Dopamine receptor D4 polymorphism predicts the effect of L-DOPA on gambling behavior. Biol Psychiatry 67:702–706CrossRefPubMedGoogle Scholar
  18. Elliot EE, Sibley DR, Katz JL (2003) Locomotor and discriminative-stimulus effects of cocaine in dopamine D5 receptor knockout mice. Psychopharmacology 169:161–168CrossRefPubMedGoogle Scholar
  19. Faraone SV, Doyle AE, Mick E, Biederman J (2001) Meta-analysis of the association between the 7-repeat allele of the dopamine D(4) receptor gene and attention deficit hyperactivity disorder. Am J Psychiatry 158:1052–1057CrossRefPubMedGoogle Scholar
  20. Ferrari M et al (2008) Dopaminergic receptor D5 mRNA expression is increased in circulating lymphocytes of Tourette syndrome patients. J Psychiatr Res 43:24–29CrossRefPubMedGoogle Scholar
  21. Filip M, Thomas ML, Cunningham KA (2000) Dopamine D5 receptors in nucleus accumbens contribute to the detection of cocaine in rats. J Neurosci 20:RC98-1–RC98-4Google Scholar
  22. Garcia MG, Puig JG, Torres RJ (2009) Abnormal adenosine and dopamine receptor expression in lymphocytes of Lesch-Nyhan patients. Brain Behav Immun 23:1125–1131CrossRefPubMedGoogle Scholar
  23. Gardner EL, Ashby CR Jr (2000) Heterogeneity of the mesotelencephalic dopamine fibers: physiology and pharmacology. Neurosci Biobehav Rev 24:115–118CrossRefPubMedGoogle Scholar
  24. Goodarzi A, Vousooghi N, Sedaghati M, Mokri A, Zarrindast MR (2009) Dopamine receptors in human peripheral blood lymphocytes: changes in mRNA expression in opioid addiction. Eur J Pharmacol 615:218–222CrossRefPubMedGoogle Scholar
  25. Hansen A, Reiter K, Ziprian T, Jacobi A, Hoffmann A, Gosemann M, Scholze J, Lipsky PE, Dorner T (2005) Dysregulation of chemokine receptor expression and function by B cells of patients with primary Sjogren’s syndrome. Arthritis Rheum 52:2109–2119CrossRefPubMedGoogle Scholar
  26. Heidbreder C (2008) Selective antagonism at dopamine D3 receptors as a target for drug addiction pharmacotherapy: a review of preclinical evidence. CNS Neurol Disord Drug Targets 7:410–421CrossRefPubMedGoogle Scholar
  27. Holden C (2010) Psychiatry. Behavioral addictions debut in proposed DSM-V. Science 327:935CrossRefPubMedGoogle Scholar
  28. Ilani T, Ben-Shachar D, Strous RD, Mazor M, Sheinkman A, Kotler M, Fuchs S (2001) A peripheral marker for schizophrenia: increased levels of D3 dopamine receptor mRNA in blood lymphocytes. Proc Natl Acad Sci USA 98:625–628PubMedCentralCrossRefPubMedGoogle Scholar
  29. Khan ZU, Gutierrez A, Martin R, Penafiel A, Rivera A, de la Calle A (2000) Dopamine D5 receptors of rat and human brain. Neuroscience 100:689–699CrossRefPubMedGoogle Scholar
  30. Kim SH, Baik SH, Park CS, Kim SJ, Choi SW, Kim SE (2011) Reduced striatal dopamine D2 receptors in people with Internet addiction. Neuroreport 22:407–411CrossRefPubMedGoogle Scholar
  31. Kirillova GP, Hrutkay RJ, Shurin MR, Shurin GV, Tourkova IL, Vanyukov MM (2008) Dopamine receptors in human lymphocytes: radioligand binding and quantitative RT-PCR assays. J Neurosci Methods 174:272–280PubMedCentralCrossRefPubMedGoogle Scholar
  32. Knight R (1996) Contribution of human hippocampal region to novelty detection. Nature 383:256–259CrossRefPubMedGoogle Scholar
  33. Kwak YT, Koo MS, Choi CH, Sunwoo I (2001) Change of dopamine receptor mRNA expression in lymphocyte of schizophrenic patients. BMC Med Genet 2:3PubMedCentralCrossRefPubMedGoogle Scholar
  34. Le Foll B, Diaz J, Sokoloff P (2003) Increased dopamine D3 receptor expression accompanying behavioral sensitization to nicotine in rats. Synapse 47:176–183CrossRefPubMedGoogle Scholar
  35. Le Fur G, Meininger V, Phan T, Gerard A, Baulac M, Uzan A (1980) Decrease in lymphocyte [3H]spiroperidol binding sites in Parkinsonism. Life Sci 27:1587–1591CrossRefPubMedGoogle Scholar
  36. Li T et al (1997) Association analysis of the dopamine D4 gene exon III VNTR and heroin abuse in Chinese subjects. Mol Psychiatry 2:413–416CrossRefPubMedGoogle Scholar
  37. Li Y et al (2006) The effect of dopamine D2, D5 receptor and transporter (SLC6A3) polymorphisms on the cue-elicited heroin craving in Chinese. Am J Med Genet B Neuropsychiatr Genet 141B:269–273CrossRefPubMedGoogle Scholar
  38. Mash DC, Staley JK (1999) D3 dopamine and kappa opioid receptor alterations in human brain of cocaine-overdose victims. Ann N Y Acad Sci 877:507–522CrossRefPubMedGoogle Scholar
  39. Mehler-Wex C, Duvigneau JC, Hartl RT, Ben-Shachar D, Warnke A, Gerlach M (2006) Increased mRNA levels of the mitochondrial complex I 75-kDa subunit. A potential peripheral marker of early onset schizophrenia? Eur Child Adolesc Psychiatry 15:504–507CrossRefPubMedGoogle Scholar
  40. Nagai Y, Ueno S, Saeki Y, Soga F, Hirano M, Yanagihara T (1996) Decrease of the D3 dopamine receptor mRNA expression in lymphocytes from patients with Parkinson’s disease. Neurology 46:791–795CrossRefPubMedGoogle Scholar
  41. Perez de Castro I, Ibanez A, Torres P, Saiz-Ruiz J, Fernandez-Piqueras J (1997) Genetic association study between pathological gambling and a functional DNA polymorphism at the D4 receptor gene. Pharmacogenetics 7:345–348PubMedGoogle Scholar
  42. Pfaffl MW, Horgan GW, Dempfle L (2002) Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res 30:e36PubMedCentralCrossRefPubMedGoogle Scholar
  43. Potenza MN (2006) Should addictive disorders include non-substance-related conditions? Addiction 101(Suppl 1):142–151CrossRefPubMedGoogle Scholar
  44. Potenza MN (2008) Review. The neurobiology of pathological gambling and drug addiction: an overview and new findings. Philos Trans R Soc Lond B Biol Sci 363:3181–3189PubMedCentralCrossRefPubMedGoogle Scholar
  45. Potenza MN, Fiellin DA, Heninger GR, Rounsaville BJ, Mazure CM (2002) Gambling: an addictive behavior with health and primary care implications. J Gen Intern Med 17:721–732PubMedCentralCrossRefPubMedGoogle Scholar
  46. Primus RJ et al (1997) II. Localization and characterization of dopamine D4 binding sites in rat and human brain by use of the novel, D4 receptor-selective ligand [3H]NGD 94-1. J Pharmacol Exp Ther 282:1020–1027PubMedGoogle Scholar
  47. Rao PA, Pickar D, Gejman PV, Ram A, Gershon ES, Gelernter J (1994) Allelic variation in the D4 dopamine receptor (DRD4) gene does not predict response to clozapine. Arch Gen Psychiatry 51:912–917CrossRefPubMedGoogle Scholar
  48. Ricci A, Amenta F (1994) Dopamine D5 receptors in human peripheral blood lymphocytes: a radioligand binding study. J Neuroimmunol 53:1–7CrossRefPubMedGoogle Scholar
  49. Ricci A, Veglio F, Amenta F (1995) Radioligand binding characterization of putative dopamine D3 receptor in human peripheral blood lymphocytes with [3H]7-OH-DPAT. J Neuroimmunol 58:139–144CrossRefPubMedGoogle Scholar
  50. Ricci A, Bronzetti E, Felici L, Tayebati SK, Amenta F (1997) Dopamine D4 receptor in human peripheral blood lymphocytes: a radioligand binding assay study. Neurosci Lett 229:130–134CrossRefPubMedGoogle Scholar
  51. Rivera A, Cuellar B, Giron FJ, Grandy DK, de la Calle A, Moratalla R (2002) Dopamine D4 receptors are heterogeneously distributed in the striosomes/matrix compartments of the striatum. J Neurochem 80:219–229CrossRefPubMedGoogle Scholar
  52. Rocc P et al (2002) Decrease of the D4 dopamine receptor messenger RNA expression in lymphocytes from patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry 26:1155–1160CrossRefPubMedGoogle Scholar
  53. Santambrogio L, Lipartiti M, Bruni A, Dal Toso R (1993) Dopamine receptors on human T- and B-lymphocytes. J Neuroimmunol 45:113–119CrossRefPubMedGoogle Scholar
  54. Self DW, Barnhart WJ, Lehman DA, Nestler EJ (1996) Opposite modulation of cocaine-seeking behavior by D1- and D2-like dopamine receptor agonists. Science 271:1586–1589CrossRefPubMedGoogle Scholar
  55. Shields PG, Lerman C, Audrain J, Bowman ED, Main D, Boyd NR, Caporaso NE (1998) Dopamine D4 receptors and the risk of cigarette smoking in African-Americans and Caucasians. Cancer Epidemiol Biomarkers Prev 7:453–458PubMedGoogle Scholar
  56. Sibley DR, Monsma FJ Jr, Shen Y (1993) Molecular neurobiology of dopaminergic receptors. Int Rev Neurobiol 35:391–415CrossRefPubMedGoogle Scholar
  57. Simpson J, Vetuz G, Wilson M, Brookes KJ, Kent L (2010) The DRD4 receptor Exon 3 VNTR and 5′ SNP variants and mRNA expression in human post-mortem brain tissue. Am J Med Genet B Neuropsychiatr Genet 153B:1228–1233PubMedGoogle Scholar
  58. Sobik L, Hutchison K, Craighead L (2005) Cue-elicited craving for food: a fresh approach to the study of binge eating. Appetite 44:253–261CrossRefPubMedGoogle Scholar
  59. Staley JK, Mash DC (1996) Adaptive increase in D3 dopamine receptors in the brain reward circuits of human cocaine fatalities. J Neurosci 16:6100–6106PubMedGoogle Scholar
  60. Straub RE, Sullivan PF, Ma Y, Myakishev MV, Harris-Kerr C, Wormley B, Kadambi B, Sadek H, Silverman MA, Webb BT et al (1999) Susceptibility genes for nicotine dependence: a genome scan and followup in an independent sample suggest that regions on chromosomes 2, 4, 10, 16, 17 and 18 merit further study. Mol Psychiatry 4:129–144CrossRefPubMedGoogle Scholar
  61. Sullivan PF, Neale MC, Silverman MA, Harris-Kerr C, Myakishev MV, Wormley B, Webb BT, Ma Y, Kendler KS, Straub RE (2001) An association study of DRD5 with smoking initiation and progression to nicotine dependence. Am J Med Genet 105:259–265CrossRefPubMedGoogle Scholar
  62. Sunahara RK et al (1991) Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature 350:614–619CrossRefPubMedGoogle Scholar
  63. Suzuki T, Kobayashi K, Nagatsu T (1995) Genomic structure and tissue distribution of the mouse dopamine D4 receptor. Neurosci Lett 199:69–72CrossRefPubMedGoogle Scholar
  64. Swant J, Chirwa S, Stanwood G, Khoshbouei H (2010) Methamphetamine reduces LTP and increases baseline synaptic transmission in the CA1 region of mouse hippocampus. PLoS One 5:e11382PubMedCentralCrossRefPubMedGoogle Scholar
  65. Vanyukov MM, Moss HB, Gioio AE, Hughes HB, Kaplan BB, Tarter RE (1998) An association between a microsatellite polymorphism at the DRD5 gene and the liability to substance abuse: pilot study. Behav Genet 28:75–82CrossRefPubMedGoogle Scholar
  66. Vogel M, Pfeifer S, Schaub RT, Grabe HJ, Barnow S, Freyberger HJ, Cascorbi I (2004) Decreased levels of dopamine D3 receptor mRNA in schizophrenic and bipolar patients. Neuropsychobiology 50:305–310CrossRefPubMedGoogle Scholar
  67. Waters N, Svensson K, Haadsma-Svensson SR, Smith MW, Carlsson A (1993) The dopamine D3-receptor: a postsynaptic receptor inhibitory on rat locomotor activity. J Neural Transm Gen Sect 94:11–19CrossRefPubMedGoogle Scholar
  68. Weinstein AM (2010) Computer and video game addiction-a comparison between game users and non-game users. Am J Drug Alcohol Abuse 36:268–276CrossRefPubMedGoogle Scholar
  69. Widyanto L, McMurran M (2004) The psychometric properties of the internet addiction test. Cyberpsychol Behav 7:443–450CrossRefPubMedGoogle Scholar
  70. Wise RA, Rompre PP (1989) Brain dopamine and reward. Annu Rev Psychol 40:191–225CrossRefPubMedGoogle Scholar
  71. Young KS (1996) Psychology of computer use: XL. Addictive use of the Internet: a case that breaks the stereotype. Psychol Rep 79:899–902CrossRefPubMedGoogle Scholar
  72. Zvara A, Szekeres G, Janka Z, Kelemen JZ, Cimmer C, Santha M, Puskas LG (2005) Over-expression of dopamine D2 receptor and inwardly rectifying potassium channel genes in drug-naive schizophrenic peripheral blood lymphocytes as potential diagnostic markers. Dis Markers 21:61–69PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  • Nasim Vousooghi
    • 1
    • 2
    Email author
  • Seyed Zeinolabedin Zarei
    • 2
    • 3
  • Mitra-Sadat Sadat-Shirazi
    • 1
    • 2
  • Fatemeh Eghbali
    • 4
  • Mohammad Reza Zarrindast
    • 2
    • 5
    • 6
    • 7
  1. 1.Department of Neuroscience, School of Advanced Technologies in MedicineTehran University of Medical SciencesTehranIran
  2. 2.Iranian National Center for Addiction Studies (INCAS), Iranian Institute for Reduction of High-Risk BehaviorsTehran University of Medical SciencesTehranIran
  3. 3.Department of NeuroscienceMedical University of ViennaViennaAustria
  4. 4.Department of Emergency, Namazi HospitalShiraz University of Medical SciencesShirazIran
  5. 5.Department of Pharmacology, School of MedicineTehran University of Medical SciencesTehranIran
  6. 6.Institute for Studies in Theoretical Physics and Mathematics, School of Cognitive SciencesTehranIran
  7. 7.Institute for Cognitive Science StudiesTehranIran

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