Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-23T16:18:14.307Z Has data issue: false hasContentIssue false
  • English
  • Français

Perspectives on Current Directions in the Neurobiology of Addiction Disorders Relevant to Genetic Risk Factors

Published online by Cambridge University Press:  07 November 2014

Yasmin L. Hurd
Get access Rights & Permissions [Opens in a new window]

Abstract

There is a significant heritability of drug addiction disorders, but potential genes that may underlie such vulnerability have not been clearly identified. Common neurobiological candidates for drug abuse include genes related to dopamine, opioid neuropeptide, and glutamate transmission that play important roles in drug reward and inhibitory control. This article provides an overview of genetic polymorphisms linked to these neurobiological systems, particularly in relation to psychostimulant- and opioid-addiction vulnerability.

Type
Review Article
Information
CNS Spectrums , Volume 11 , Issue 11 , November 2006 , pp. 855 - 862
Copyright
Copyright © Cambridge University Press 2006

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1. Goldman, D, Oroszi, G, Ducci, F. The genetics of addictions: uncovering the genes. Nat Rev Genet. 2005;6:521–532.Google Scholar
2. Tsuang, MT, Lyons, MJ, Meyer, JM, et al. Co-occurrence of abuse of different drugs in men: the role of drug-specific and shared vulnerabilities. Arch Gen Psychiatry. 1998;55:967–972.Google Scholar
3. Merikangas, KR, Stolar, M, Stevens, DE, et al. Familial transmission of substance use disorders. Arch Gen Psychiatry. 1998;55:973–979.Google Scholar
4. Ungless, MA. Dopamine: the salient issue. Trends Neurosci. 2004;27:702–706.Google Scholar
5. McClure, SM, Daw, ND, Montague, PR. A computational substrate for incentive salience. Trends Neurosci. 2003;26:423–428.Google Scholar
6. Haber, SN, Ryoo, H, Cox, C, Lu, W. Subsets of midbrain dopaminergic neurons in monkeys are distinguished by different levels of mRNA for the dopamine transporter: comparison with the mRNA for the D2 receptor, tyrosine hydroxylase and calbindin immunoreactivity. J Comp Neurol. 1995;362:400–410.Google Scholar
7. Zahm, DS, Brog, JS. On the significance of subterritories in the “accumbens” part of the rat ventral striatum. Neuroscience. 1992;50:751–767.Google Scholar
8. Groenewegen, HJ, Wright, CI, Beijer, AV. The nucleus accumbens: gateway for limbic structures to reach the motor system? Prog Brain Res. 1996;107:485–511.Google Scholar
9. Cragg, SJ, Rice, ME. DAncing past the DAT at a DA synapse. Trends Neurosci. 2004;27:270–277.Google Scholar
10. Hitri, A, Hurd, YL, Wyatt, RJ, Deutsch, SI. Molecular, functional and biochemical characteristics of the dopamine transporter: regional differences and clinical relevance. Clin Neuropharmacol. 1994;17:1–22.Google Scholar
11. Amara, SG, Kuhar, MJ. Neurotransmitter transporters: recent progress. Annu Rev Neurosci. 1993;16:73–93.Google Scholar
12. Vandenbergh, DJ, Persico, AM, Hawkins, AL, et al. Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTR. Genomics. 1992;14:1104–1106.Google Scholar
13. Gelemter, J, Kranzler, H, Lacobelle, J. Population studies of polymorphisms at loci of neuropsychiatric interest (tryptophan hydroxylase (TPH), dopamine transporter protein (SLC6A3), D3 dopamine receptor (DRD3), apolipoprotein E (APOE), mu opioid receptor (OPRM1), and ciliary neurotrophic factor (CNTF)). Genomics. 1998;52:289–297.Google Scholar
14. Jacobsen, LK, Staley, JK, Zoghbi, SS, et al. Prediction of dopamine transporter binding availability by genotype: a preliminary report. Am J Psychiatry. 2000;157:1700–1703.Google Scholar
15. Heinz, A, Goldman, D, Jones, DW, et al. Genotype influences in vivo dopamine transporter availability in human striatum. Neuropsychopharmacology 2000;22:133–139.Google Scholar
16. Martinez, D, Gelernter, J, Abi-Dargham, A et al. The variable number of tandem repeats polymorphism of the dopamine transporter gene is not associated with significant change in dopamine transporter phenotype in humans. Neuropsychopharmacology. 2001;24:553–560.Google Scholar
17. Gelernter, J, Kranzler, HR, Satel, SL, Rao, PA. Genetic association between dopamine transporter protein alleles and cocaine-induced paranoia. Neuropsychopharmacology. 1994;11:195–200.Google Scholar
18. Liu, HC, Lin, SK, Liu, SK, et al. DAT polymorphism and diverse clinical manifestations in methamphetamine abusers. Psychiatr Genet. 2004;14:33–37.Google Scholar
19. Hong, CJ, Cheng, CY, Shu, LR, Yang, CY, Tsai, SJ. Association study of the dopamine and serotonin transporter genetic polymorphisms and methamphetamine abuse in Chinese males. J Neural Transm. 2003;110:345–351.Google Scholar
20. Guindalini, C, Howard, M, Haddley, K, et al. A dopamine transporter gene functional variant associated with cocaine abuse in a Brazilian sample. Proc Natl Acad Sci U S A. 2006;103:4552–4557.Google Scholar
21. Ujike, H, Harano, M, Inada, T, et al. Nine- or fewer repeat alleles in VNTR polymorphism of the dopamine transporter gene is a strong risk factor for prolonged methamphetamine psychosis. Pharmacogenomics J. 2003;3:242–247.Google Scholar
22. Johnson, SW, North, RA. Opioids excite dopamine neurons by hyperpolarization of local interneurons. J Neurosci. 1992;12:483–488.Google Scholar
23. Gerra, G, Garofano, L, Pellegrini, C, et al. Allelic association of a dopamine transporter gene polymorphism with antisocial behaviour in heroin-dependent patients. Addict Biol. 2005;10:275–281.Google Scholar
24. Galeeva, AR Gareeva, AE, lur'ev, EG, et al. VNTR polymorphisms of the serotonin transporter and dopamine transporter genes in male opiate addicts [Russian]. Mol Biol(Mosk). 2002;36:593–598.Google Scholar
25. Volkow, ND, Fowler, JS, Wang, GJ, et al. Role of dopamine, the frontal cortex and memory circuits in drug addiction: insight from imaging studies. Neurobiol Learn Mem. 2002;78:610–624.Google Scholar
26. Nader, MA, Morgan, D, Gage, HD, et al. PET imaging of dopamine D2 receptors during chronic cocaine self-administration in monkeys. Nat Neurosci. 2006;9:1050–1056.Google Scholar
27. Noble, EP, Blum, K, Ritchie, T, Montgomery, A, Sheridan, PJ, et al. Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. Arch Gen Psychiatry. 1991;48:648–654.Google Scholar
28. Noble, EP. D2 dopamine receptor gene in psychiatric and neurologic disorders and its phenotypes. Am J Med Genet B Neuropsychiatr Genet. 2003;116:103–125.Google Scholar
29. Neville, MJ, Johnstone, EC, Walton, RT. Identification and characterization of ANKK1: a novel kinase gene closely linked to DRD2 on chromosome band 11q23.1. Hum Mutat. 2004;23:540–545.Google Scholar
30. Persico, AM, Bird, G, Gabbay, FH, Uhl, GR, et al. D2 dopamine receptor gene Taql A1 and B1 restriction fragment length polymorphisms: enhanced frequencies in psychostimulant-preferring polysubstance abusers. Biol Psychiatry. 1996;40:776–784.Google Scholar
31. Comings, DE, Gonzalez, N, Wu, S, et al. Homozygosity at the dopamine DRD3 receptor gene in cocaine dependence. Mol Psychiatry. 1999;4:484–487.Google Scholar
32. Gelernter, J, Kranzler, H, Satel, SL. No association between D2 dopamine receptor (DRD2) alleles or haplotypes and cocaine dependence or severity of cocaine dependence in European- and African-Americans. Biol Psychiatry. 1999;45:340–345.Google Scholar
33. Lawford, BR, Young, RM, Noble, EP, et al. The D(2) dopamine receptor A(1) allele and opioid dependence: association with heroin use and response to methadone treatment. Am J Med Genet. 2000;96:592–598.Google Scholar
34. Shahmoradgoli Najafabadi, M, Ohadi, M, Joghataie, MT, et al. Association between the DRD2 A1 allele and opium addiction in the Iranian population. Am J Med Genet B Neuropsychiatr Genet. 2005;134:39–41.Google Scholar
35. Xu, K, Lichtermann, D, Lipsky, RH, et al. Association of specific haplotypes of D2 dopamine receptor gene with vulnerability to heroin dependence in 2 distinct populations. Arch Gen Psychiatry. 2004;61:597–606.Google Scholar
36. Suzuki, M, Hurd, YL, Sokoloff, P, Schwartz, JC, Sedvall, G. D3 dopamine receptor mRNA is widely expressed in the human brain. Brain Res. 1998;779:58–74.Google Scholar
37. Murray, AM, Ryoo, HL, Gurevich, E, Joyce, JN. Localization of dopamine D3 receptors to mesolimbic and D2 receptors to mesostriatal regions of human forebrain. Proc Natl Acad Sci U S A. 1994;91:11271–11275.Google Scholar
38. Chen, J, Marmur, R, Paredes, W, Pulles, A, Gardner, EL. Systemic cocaine challenge after chronic cocaine treatment reveals sensitization of extracellular dopamine levels in nucleus accumbens but direct cocaine perfusion into nucleus accumbens does not: implications for the neural locus of cocaine sensitization. Life Sci. 1996;58:PL139–PL146.Google Scholar
39. Ebstein, RP, Novick, O, Umansky, R, et al. Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking. Nat Genet. 1996;12:78–80.Google Scholar
40. Schinka, JA, Letsch, EA, Crawford, FC. DRD4 and novelty seeking: results of meta-analyses. Am J Med Genet. 2002;114:643–648.Google Scholar
41. Lee, HJ, Lee, HS, Kim, YK, et al. D2 and D4 dopamine receptor gene polymorphisms and personality traits in a young Korean population. Am J Med Genet B Neuropsychiatr Genet. 2003;121:44–49.Google Scholar
42. Kotler, M, Cohen, H, Segman, R, et al. Excess dopamine D4 receptor (D4DR) exon III seven repeat allele in opioid-dependent subjects. Mol Psychiatry. 1997;2:251–254.Google Scholar
43. Li, T, Zhu, ZH, Liu, X, et al. Association analysis of polymorphisms in the DRD4 gene and heroin abuse in Chinese subjects. Am J Med Genet. 2000;96:616–621.Google Scholar
44. Li, T, Xu, K, Deng, H, et al. Association analysis of the dopamine D4 gene exon III VNTR and heroin abuse in Chinese subjects. Mol Psychiatry. 1997;2:413–416.Google Scholar
45. Li, T, Chen, CK, Hu, X, et al. Association analysis of the DRD4 and COMT genes in methamphetamine abuse. Am J Med Genet B Neuropsychiatr Genet. 2004;129:120–124.Google Scholar
46. Duaux, E, Gorwood, P, Griffon, N, et al. Homozygosity at the dopamine D3 receptor gene is associated with opiate dependence. Mol Psychiatry. 1998;3:333–336.Google Scholar
47. Robinson, TE, Berridge, KC. Incentive-sensitization and addiction. Addiction. 2001;96:103–114.Google Scholar
48. Li, Y, Shao, C, Zhang, D, et al. 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. 2006;141:269–273.Google Scholar
49. Shao, C, Li, Y, Jiang, K, et al. Dopamine D4 receptor polymorphism modulates cueelicited heroin craving in Chinese. Psychopharmacology (Berl). 2006;186:185–190.Google Scholar
50. Herz, A. Opioid reward mechanisms: a key role in drug abuse? Can J Physiol Pharmacol. 1998;76:252–258.Google Scholar
51. Kieffer, BL, Gaveriaux-Ruff, C. Exploring the opioid system by gene knockout. Prog Neurobiol. 2002;66:285–306.Google Scholar
52. Kelley, AE, Bakshi, VP, Haber, SN, Steininger, TL, Will, MJ, Zhang, M. Opioid modulation of taste hedonics within the ventral striatum. Physiol Behav. 2002;76:365–377.Google Scholar
53. Pecina, S, Berridge, KC. Hedonic hot spot in nucleus accumbens shell: where do mu-opioids cause increased hedonic impact of sweetness? J Neurosci. 2005;25:11777–11786.Google Scholar
54. Bond, C, LaForge, KS, Tian, M, et al. Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci U S A. 1998;95:9608–9613.Google Scholar
55. Zhang, Y, Wang, D, Johnson, AD, Papp, AC, Sadee, W. Allelic expression imbalance of human mu opioid receptor (OPRM1) caused by variant A118G. J Biol Chem. 2005;280:32618–32624.Google Scholar
56. Drakenberg, K, Nikoshkov, A, Horvath, MC, et al. Mu opioid receptor A118G polymorphism in association with striatal opioid neuropeptide gene expression in heroin abusers. Proc Natl Acad Sci U S A. 2006;103:7883–7888.Google Scholar
57. Bart, G, Laforge, KS, Borg, L, Lilly, C, Ho, A, Kreek, MJ. Altered Levels of Basal Cortisol in Healthy Subjects with a 118G Allele in Exon 1 of the Mu Opioid Receptor Gene. Neuropsychopharmacology. 2006;31:2313–2317.Google Scholar
58. Luo, X, Kranzler, HR, Zhao, H, Gelernter, J. Haplotypes at the OPRM1 locus are associated with susceptibility to substance dependence in European-Americans. Am J Med Genet B Neuropsychiatr Genet. 2003;120:97–108.Google Scholar
59. Arias, A, Feinn, R, Kranzler, HR. Association of an Asn40Asp (A118G) polymorphism in the mu-opioid receptor gene with substance dependence: a meta-analysis. Drug Alcohol Depend. 2006;83:262–268.Google Scholar
60. Gelernter, J, Kranzler, H, Cubells, J. Genetics of two mu opioid receptor gene (OPRM1) exon I polymorphisms: population studies, and allele frequencies in alcohol- and drug-dependent subjects. Mol Psychiatry. 1999;4:476–483.Google Scholar
61. Crowley, JJ, Oslin, DW, Patkar, AA, et al. A genetic association study of the mu-opioid receptor and severe opioid dependence. Psychiatr Genet. 2003;13:169–173.Google Scholar
62. Franke, P, Wang, T, Nothen, MM, et al. Nonreplication of association between mu-opioid-receptor gene (OPRM1) A118G polymorphism and substance dependence. Am J Med Genet. 2001;105:114–119.Google Scholar
63. Szeto, CY, Tang, NL, Lee, DT, Stadlin, A. Association between mu opioid receptor gene polymorphisms and Chinese heroin addicts. Neuroreport. 2001;12:1103–1106.Google Scholar
64. Tan, EC, Tan, CH, Karupathivan, U, Yap, EP, Mu opioid receptor gene polymorphisms and heroin dependence in Asian populations. Neuroreport. 2003;14:569–572.Google Scholar
65. Bart, G, Heilig, M, LaForge, KS, et al. Substantial attributable risk related to a functional mu-opioid receptor gene polymorphism in association with heroin addiction in central Sweden. Mol Psychiatry. 2004;9:547–549.Google Scholar
66. Shi, J, Hui, L, Xu, Y, Wang, F, Huang, W, Hu, G. Sequence variations in the mu-opioid receptor gene (OPRM1) associated with human addiction to heroin. Hum Mutat. 2002;19:459–460.Google Scholar
67. Ide, S, Kobayashi, H, Tanaka, K, et al. Gene polymorphisms of the mu opioid receptor in methamphetamine abusers. Ann N Y Acad Sci. 2004;1025:316–324.Google Scholar
68. Comings, DE, Blake, H, Dietz, G, et al. The proenkephalin gene (PENK) and opioid dependence. Neuroreport. 1999;10:1133–1135.Google Scholar
69. Hurd, YL, Herkenham, M. Molecular alterations in the neostriatum of human cocaine addicts. Synapse. 1993;13:357–369.Google Scholar
70. Staley, JK, Rothman, RB, Rice, KC, Partilla, J, Mash, DC. Kappa2 opioid receptors in limbic areas of the human brain are upregulated by cocaine in fatal overdose victims. J Neurosci. 1997;17:8225–8233.Google Scholar
71. Zimprich, A, Kraus, J, Woltje, M, Mayer, P, Rauch, E, Hollt, V. An allelic variation in the human prodynorphin gene promoter alters stimulus-induced expression. J Neurochem. 2000;74:472–477.Google Scholar
72. Chen, AC, LaForge, KS, Ho, A, et al. Potentially functional polymorphism in the promoter region of prodynorphin gene may be associated with protection against cocaine dependence or abuse. Am J Med Genet. 2002;114:429–435.Google Scholar
73. Dahl, JP, Weller, AE, Kampman, KM, et al. Confirmation of the association between a polymorphism in the promoter region of the prodynorphin gene and cocaine dependence. Am J Med Genet B Neuropsychiatr Genet. 2005;139:106–108.Google Scholar
74. Ray, R, Doyle, GA, Crowley, JJ, et al. A functional prodynorphin promoter polymorphism and opioid dependence. Psychiatr Genet. 2005;15:295–298.Google Scholar
75. Yuferov, V, Fussell, D, LaForge, KS, et al. Redefinition of the human kappa opioid receptor gene (OPRK1) structure and association of haplotypes with opiate addiction. Pharmacogenetics. 2004;14:793–804.Google Scholar
76. Lotta, T, Vidgren, J, Tilgmann, C, et al. Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry. 1995;34:4202–4210.Google Scholar
77. Egan, MF, Goldberg, TE, Kolachana, BS, et al. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci U S A. 2001;98:6917–6922.Google Scholar
78. Goldberg, TE, Weinberger, DR. Genes and the parsing of cognitive processes. Trends Cogn Sci. 2004;8:325–335.Google Scholar
79. Joober, R, Gauthier, J, Lai, S, et al. Catechol-O-methyltransferase Val-108/158-Met gene variants associated with performance on the Wisconsin Card Sorting Test. Arch Gen Psychiatry. 2002;59:662–663.Google Scholar
80. Blasi, G, Mattay, VS, Bertolino, A, et al. Effect of catechol-O-methyltransferase val158met genotype on attentional control. J Neurosci. 2005;25:5038–5045.Google Scholar
81. Bertolino, A, Caforio, G, Blasi, G, et al. Interaction of COMT (Val(108/158)Met) genotype and olanzapine treatment on prefrontal cortical function in patients with schizophrenia. Am J Psychiatry. 2004;161:1798–1805.Google Scholar
82. Vandenbergh, DJ, Rodriguez, LA, Miller, IT, Uhl, GR, Lachman, HM. High-activity catechol-O-methyltransferase allele is more prevalent in polysubstance abusers. Am J Med Genet. 1997;74:439–442.Google Scholar
83. Horowitz, R, Kotler, M, Shufman, E, et al. Confirmation of an excess of the high enzyme activity COMT val allele in heroin addicts in a family-based haplotype relative risk study. Am J Med Genet. 2000;96:599–603.Google Scholar
84. Biederman, J, Wilens, T, Mick, E, et al. Is ADHD a risk factor for psychoactive substance use disorders? Findings from a four-year prospective follow-up study. J Am Acad Child Adolesc Psychiatry. 1997;36:21–29.Google Scholar
85. Flory, K, Lynam, DR. The relation between attention deficit hyperactivity disorder and substance abuse: what role does conduct disorder play? Clin Child Fam Psychol Rev. 2003;6:1–16.Google Scholar
86. Faraone, SV, Doyle, AE, Mick, E, Biederman, J. 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. 2001;158:1052–1057.Google Scholar
87. Chen, CK, Hu, X, Lin, SK, et al. Association analysis of dopamine D2-like receptor genes and methamphetamine abuse. Psychiatr Genet. 2004;14:223–226.Google Scholar
88. Goldman-Rakic, PS, Muly, EC 3rd, Williams, GV. D(1) receptors in prefrontal cells and circuits. Brain Res Brain Res Rev. 2000;31:295–301.Google Scholar
89. Williams, GV, Castner, SA. Under the curve: critical issues for elucidating D1 receptor function in working memory. Neuroscience. 2006;139:263–276.Google Scholar
90. Ciccocioppo, R, Sanna, PP, Weiss, F. Cocaine-predictive stimulus induces drug-seeking behavior and neural activation in limbic brain regions after multiple months of abstinence: reversal by D(1) antagonists. Proc Natl Acad Sci U S A. 2001;98:1976–1981.Google Scholar
91. Hummel, M, Unterwald, EM. D1 dopamine receptor: a putative neurochemical and behavioral link to cocaine action. J Cell Physiol. 2002;191:17–27.Google Scholar
92. Comings, DE, Gade, R, Wu, S, et al. Studies of the potential role of the dopamine D1 receptor gene in addictive behaviors. Mol Psychiatry. 1997;2:44–56.Google Scholar
93. Liu, HC, Chen, CK, Leu, SJ, Wu, HT, Lin, SK. Association between dopamine receptor D1 A-48G polymorphism and methamphetamine abuse. Psychiatry Clin Neurosci. 2006;60:226–231.Google Scholar
94. Sunahara, RK, Guan, HC, O'Dowd, BF, et al. Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature. 1991;350:614–619.Google Scholar
95. Sherrington, R, Mankoo, B, Attwood, J, et al. Cloning of the human dopamine D5 receptor gene and identification of a highly polymorphic microsatellite for the DRD5 locus that shows tight linkage to the chromosome 4p reference marker RAF1P1. Genomics. 1993;18:423–425.Google Scholar
96. Vanyukov, MM, Moss, HB, Gioio, AE, Hughes, HB, Kaplan, BB, Tarter, RE. An association between a microsatellite polymorphism at the DRD5 gene and the liability to substance abuse: pilot study. Behav Genet. 1998;28:75–82.Google Scholar
97. Vanyukov, MM, Moss, HB, Kaplan, BB, Kirillova, GP, Tarter, RE. Antisociality, substance dependence, and the DRD5 gene: a preliminary study. Am J Med Genet. 2000;96:654–658.Google Scholar
98. Wolf, ME. The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants. Prog Neurobiol. 1998;54:679–720.Google Scholar
99. Kalivas, PW, Volkow, ND. The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry. 2005;162:1403–1413.Google Scholar
100. Szumlinski, KK, Abernathy, KE, Oleson, EB, et al. Homer isoforms differentially regulate cocaine-induced neuroplasticity. Neuropsychopharmacology. 2006;31:768–777.Google Scholar
101. Boeckers, TM, Bockmann, J, Kreutz, MR, Gundelfinger, ED. ProSAP/Shank proteins—a family of higher order organizing molecules of the postsynaptic density with an emerging role in human neurological disease. J Neurochem. 2002;81:903–910.Google Scholar
102. El-Husseini, AE, Schnell, E, Chetkovich, DM, Nicoll, RA, Bredt, DS. PSD-95 involvement in maturation of excitatory synapses. Science. 2000;290:1364–1368.Google Scholar
103. Szumlinski, KK, Kalivas, PW, Worley, PP, Homer proteins: implications for neuropsychiatric disorders. Curr Opin Neurobiol. 2006;16:251–257.Google Scholar