Abstract
The dopaminergic system plays a pivotal role in the central nervous system via its five diverse receptors (D1–D5). Dysfunction of dopaminergic system is implicated in many neuropsychological diseases, including attention deficit hyperactivity disorder (ADHD), a common mental disorder that prevalent in childhood. Understanding the relationship of five different dopamine (DA) receptors with ADHD will help us to elucidate different roles of these receptors and to develop therapeutic approaches of ADHD. This review summarized the ongoing research of DA receptor genes in ADHD pathogenesis and gathered the past published data with meta-analysis and revealed the high risk of DRD5, DRD2, and DRD4 polymorphisms in ADHD.
This is a preview of subscription content, access via your institution.




References
- 1.
Tannock R (1998) Attention deficit hyperactivity disorder: advances in cognitive, neurobiological, and genetic research. J Child Psychol Psychiatry 39(1):65–99
- 2.
Baumgartel A, Wolraich ML, Dietrich M (1995) Comparison of diagnostic criteria for attention deficit disorders in a German elementary school sample. J Am Acad Child Adolesc Psychiatry 34:629–638
- 3.
Anderson JC, Williams S, McGee R, Silva PA (1987) DSMIII-R disorders in preadolescent children: prevalence in a large sample from the general population. Arch Gen Psychiatry 44:69–76
- 4.
Barkley RA, Smith KM, Fischer M, Navia B (2006) An examination of the behavioral and neuropsychological correlates of three ADHD candidate gene polymorphisms (DRD4 7+, DBH TaqI A2, and DAT1 40 bp VNTR) in hyperactive and normal children followed to adulthood. Am J Med Genet B Neuropsychiatr Genet 141B(5):487–498
- 5.
Biederman J, Newcorn J, Sprich S (1991) Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders. Am J Psychiatry 148:564–577
- 6.
Gittelman R, Mannuzza S, Shenker R, Bonagura N (1985) Hyperactive boys almost grown up. I. Psychiatric status. Arch Gen Psychiatry 42(10):937–947
- 7.
Swanson JM, Sergeant JA, Taylor E, Sonuga-Barke E, Jensen PS, Cantwell DP (1998) Attention-deficit hyperactivity disorder and hyperkinetic disorder. Lancet 351(9100):429–433
- 8.
Wilens TE, Biederman J, Spencer TJ (2002) Attention deficit/hyperactivity disorder across the lifespan. Annu Rev Med 53:113–131
- 9.
Woodward L, Taylor E, Dowdney L (1998) The parenting and family functioning of children with hyperactivity. J Child Psychol Psychiatry 39:161–169
- 10.
Barkley RA (1990) Attention deficit hyperactivity disorder: a handbook for diagnosis and treatment. Guilford, New York
- 11.
Mannuzza S, Klein RG, Bessler A, Malloy P, LaPadula M (1993) Adult outcome of hyperactive boys. Educational achievement, occupational rank, and psychiatric status. Arch Gen Psychiatry 50(7):565–576
- 12.
Lilienfeld SO, Waldman ID (1990) The relation between childhood attention-deficit hyperactivity disorder and adult antisocial behavior reexamined: the problem of heterogeneity. Clin Psychol Rev 10(6):699–725
- 13.
Loeber R, Dishion T (1983) Early predictors of male delinquency: a review. Psychol Bull 94(1):68–99
- 14.
Biederman J, Faraone SV (2005) Attention-deficit hyperactivity disorder. Lancet 366:237–248
- 15.
Spencer T, Biederman J, Wilens T (1999) Attention-deficit/hyperactivity disorder and comorbidity. Pediatr Clin N Am 46:915–927
- 16.
Jensen PS, Martin D, Cantwel LD (1997) Comorbidity in ADHD: implications for research, practice and DSMIV. J Am Acad Child Adolesc Psychiatry 36(7):1065–1079
- 17.
Bird HR, Gould MS, Staghezza BM (1993) Patterns of diagnostic comorbidity in a community sample of children aged 9 through 16 years. J Am Acad Child Adolesc Psychiatry 32(2):361–368
- 18.
Faraone SV, Perlis RH, Doyle AE, Smoller JW, Goralnick JJ, Holmgren MA, Sklar P (2005) Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry 57(11):1313–1323
- 19.
Derks EM, Hudziak JJ, Dolan CV, van Beijsterveldt TC, Verhulst FC, Boomsma DI (2008) Genetic and environmental influences on the relation between attention problems and attention deficit hyperactivity disorder. Behav Genet 38(1):11–23
- 20.
Haberstick BC, Timberlake D, Hopfer CJ, Lessem JM, Ehringer MA, Hewitt JK (2008) Genetic and environmental contributions to retrospectively reported DSM-IV childhood attention deficit hyperactivity disorder. Psychol Med 38(7):1057–1066
- 21.
Wood AC, Rijsdijk F, Saudino KJ, Asherson P, Kuntsi J (2008) High heritability for a composite index of children's activity level measures. Behav Genet 38(3):266–276
- 22.
Bobb AJ, Addington AM, Sidransky E, Gornick MC, Lerch JP, Greenstein DK, Clasen LS, Sharp WS, Inoff-Germain G, Wavrant-De VF, Arcos-Burgos M, Straub RE, Hardy JA, Castellanos FX, Rapoport JL (2005) Support for association between ADHD and two candidate genes: NET1 and DRD1. Am J Med Genet B Neuropsychiatr Genet 134B(1):67–72
- 23.
Banaschewski T, Becker K, Scherag S, Franke B, Coghill D (2010) Molecular genetics of attention-deficit/hyperactivity disorder: an overview. Eur Child Adolesc Psychiatry 19(3):237–257
- 24.
Gizer IR, Ficks C, Waldman ID (2009) Candidate gene studies of ADHD: a meta-analytic review. Hum Genet 126(1):51–90
- 25.
Sibley DR, Monsma FJ Jr (1992) Molecular biology of dopamine receptors. Trends Pharmacol Sci 13:61–69
- 26.
Gingrich JA, Caron MG (1993) Recent advances in the molecular biology of dopamine receptors. Annu Rev Neurosci 16:299–321
- 27.
Cichon S, Nöthen MM, Stöber G, Schroers R, Albus M, Maier W, Rietschel M, Körner J, Weigelt B, Franzek E et al (1996) Systematic screening for mutations in the 5′-regulatory region of the human dopamine D1 receptor (DRD1) gene in patients with schizophrenia and bipolar affective disorder. Am J Med Genet 67(4):424–428
- 28.
Pivonello R, Ferone D, Lombardi G, Colao A, Lamberts SW, Hofland LJ (2007) Novel insights in dopamine receptor physiology. Eur J Endocrinol 156(Suppl 1):S13–S21
- 29.
Fukunaga K, Shioda N (2012) Novel dopamine D2 receptor signaling through proteins interacting with the third cytoplasmic loop. Mol Neurobiol 45(1):144–152
- 30.
Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (1998) Dopamine receptors: from structure to function. Physiol Rev 78(1):189–225
- 31.
Vallone D, Picetti R, Borrelli E (2000) Structure and function of dopamine receptors. Neurosci Biobehav Rev 24(1):125–132
- 32.
Gloerich M, Bos JL (2010) Epac: defining a new mechanism for cAMP action. Annu Rev Pharmacol Toxicol 50:355–375
- 33.
Schultz W, Dayan P, Montague PR (1997) A neural substrate of prediction and reward. Science 275(5306):1593–1599
- 34.
Beninger RJ, Miller R (1998) Dopamine D1-like receptors and reward-related incentive learning. Neurosci Biobehav Rev 22(2):335–345
- 35.
Hollerman JR, Schultz W (1998) Dopamine neurons report an error in the temporal prediction of reward during learning. Nat Neurosci 1(4):304–309
- 36.
Iversen SD (1995) Interactions between excitatory amino acids and dopamine systems in the forebrain: implications for schizophrenia and Parkinson's disease. Behav Pharmacol 6(5 And 6):478–491
- 37.
Picetti R, Saiardi A, Abdel ST, Bozzi Y, Baik JH, Borrelli E (1997) Dopamine D2 receptors in signal transduction and behavior. Crit Rev Neurobiol 11(2–3):121–142
- 38.
Watanabe M, Kodama T, Hikosaka K (1997) Increase of extracellular dopamine in primate prefrontal cortex during a working memory task. J Neurophysiol 78(5):2795–2798
- 39.
Hietala J, Syvalahti E (1996) Dopamine in schizophrenia. Ann Med 28:557–561
- 40.
Baldessarini RJ (1997) Dopamine receptors and clinical medicine. In: Neve KA, Neve RL (eds) The Dopamine Receptors. Humana Press, NJ, pp 457–498
- 41.
Bardo MT (1998) Neuropharmacological mechanisms of drug reward: beyond dopamine in the nucleus accumbens. Crit Rev Neurobiol 12(1–2):37–67
- 42.
Nestler EJ (1997) Molecular mechanisms of opiate and cocaine addiction. Curr Opin Neurobiol 7(5):713–719
- 43.
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(5255):1586–1589
- 44.
Wise RA (1996) Neurobiology of addiction. Curr Opin Neurobiol 6(2):243–251
- 45.
Donnan GA, Woodhouse DG, Kaczmarczyk SJ, Holder JE, Paxinos G, Chilco PJ, Churchyard AJ, Kalnins RM, Fabinyi GC, Mendelsohn FA (1991) Evidence for plasticity of the dopaminergic system in parkinsonism. Mol Neurobiol 5(2–4):421–433
- 46.
Yu S, Ueda K, Chan P (2005) α-Synuclein and dopamine metabolism. Mol Neurobiol 31(1):243–254
- 47.
Seiden LS, Sabol KE, Ricaurte GA (1993) Amphetamine: effects on catecholamine systems and behavior. Annu Rev Pharmacol Toxicol 33:639–677
- 48.
Robertson SD, Matthies HJ, Galli A (2009) A closer look at amphetamine-induced reverse transport and trafficking of the dopamine and norepinephrine transporters. Mol Neurobiol 39(2):73–80
- 49.
Safer DJ, Krager JM (1988) A survey of medication treatment for hyperactive/inattentive students. JAMA 260(15):2256–2258
- 50.
Sidhu A, Niznik HB (2000) Coupling of dopamine receptor subtypes to multiple and diverse G proteins. Int J Dev Neurosci 18(7):669–677
- 51.
Grandy DK, Zhou QY, Allen L, Litt R, Magenis RE, Civelli O, Litt M (1990) A human D1 dopamine receptor gene is located on chromosome 5 at q35.1 and identifies an EcoRI RFLP. Am J Hum Genet 47(5):828–834
- 52.
Jin LQ, Wang HY, Friedman E (2001) Stimulated D(1) dopamine receptors couple to multiple Galpha proteins in different brain regions. J Neurochem 78(5):981–990
- 53.
Wang HY, Undie AS, Friedman E (1995) Evidence for the coupling of Gq protein to D1-like dopamine sites in rat striatum: possible role in dopamine-mediated inositol phosphate formation. Mol Pharmacol 48(6):988–994
- 54.
Bergson C, Mrzljak L, Smiley JF, Pappy M, Levenson R, Goldman-Rakic PS (1995) Regional, cellular, and subcellular variations in the distribution of D1 and D5 dopamine receptors in primate brain. J Neurosci 15(12):7821–7836
- 55.
Paul ML, Graybiel AM, David JC, Robertson HA (1992) D1-like and D2-like dopamine receptors synergistically activate rotation and c-fos expression in the dopamine-depleted striatum in a rat model of Parkinson's disease. J Neurosci 12(10):3729–3742
- 56.
Drago J, Gerfen CR, Lachowicz JE, Steiner H, Hollon TR, Love PE, Ooi GT, Grinberg A, Lee EJ, Huang SP, Et A (1994) Altered striatal function in a mutant mouse lacking D1A dopamine receptors. Proc Natl Acad Sci USA 91(26):12564–12568
- 57.
Xu M, Moratalla R, Gold LH, Hiroi N, Koob GF, Graybiel AM, Tonegawa S (1994) Dopamine D1 receptor mutant mice are deficient in striatal expression of dynorphin and in dopamine-mediated behavioral responses. Cell 79(4):729–742
- 58.
Crawford CA, Drago J, Watson JB, Levine MS (1997) Effects of repeated amphetamine treatment on the locomotor activity of the dopamine D1A-deficient mouse. Neuroreport 8(11):2523–2527
- 59.
Moratalla R, Xu M, Tonegawa S, Graybiel AM (1996) Cellular responses to psychomotor stimulant and neuroleptic drugs are abnormal in mice lacking the D1 dopamine receptor. Proc Natl Acad Sci USA 93(25):14928–14933
- 60.
Drago J, Padungchaichot P, Accili D, Fuchs S (1998) Dopamine receptors and dopamine transporter in brain function and addictive behaviors: insights from targeted mouse mutants. Dev Neurosci 20(2–3):188–203
- 61.
Ariano MA, Drago J, Sibley DR, Levine MS (1998) Striatal excitatory amino acid receptor subunit expression in the D1A-dopamine receptor-deficient mouse. Dev Neurosci 20(2–3):237–241
- 62.
Levine MS, Altemus KL, Cepeda C, Cromwell HC, Crawford C, Ariano MA, Drago J, Sibley DR, Westphal H (1996) Modulatory actions of dopamine on NMDA receptor-mediated responses are reduced in D1A-deficient mutant mice. J Neurosci 16(18):5870–5882
- 63.
Smith DR, Striplin CD, Geller AM, Mailman RB, Drago J, Lawler CP, Gallagher M (1998) Behavioural assessment of mice lacking D1A dopamine receptors. Neuroscience 86(1):135–146
- 64.
Arnsten AF, Steere JC, Hunt RD (1996) The contribution of alpha 2-noradrenergic mechanisms of prefrontal cortical cognitive function. Potential significance for attention-deficit hyperactivity disorder. Arch Gen Psychiatry 53(5):448–455
- 65.
Arnsten A (2001) Dopaminergic and noradrenergic influences on cognitive functions mediated by prefrontal cortex. In: Solanto MV, Arnsten A, Castellanos FX (eds) Stimulant drugs and ADHD. basic and clinical neuroscience. Oxford University Press, New York, NY, pp 185–208
- 66.
Goldman-Rakic PS, Muly ER, Williams GV (2000) D(1) receptors in prefrontal cells and circuits. Brain Res Brain Res Rev 31(2–3):295–301
- 67.
Denney CB, Rapport MD (2001) Cognitive pharmacology of stimulants in children with ADHD. Oxford University Press, Inc, New York, NY, pp 283–302
- 68.
Castellanos FX, Tannock R (2002) Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes. Nat Rev Neurosci 3(8):617–628
- 69.
Cao Y, Cui Q (2010) Association between the polymorphisms dopamine D1 receptor gene and attention deficit hyperactivity disorder. Progress in Modern Biomedicine 10(21):4039–4041
- 70.
Misener VL, Luca P, Azeke O, Crosbie J, Waldman I, Tannock R, Roberts W, Malone M, Schachar R, Ickowicz A, Kennedy JL, Barr CL (2004) Linkage of the dopamine receptor D1 gene to attention-deficit/hyperactivity disorder. Mol Psychiatry 9(5):500–509
- 71.
Cichon S, Nothen MM, Erdmann J, Propping P (1994) Detection of four polymorphic sites in the human dopamine D1 receptor gene (DRD1). Hum Mol Genet 3(1):209
- 72.
Sherrington R, Mankoo B, Attwood J, Kalsi G, Curtis D, Buetow K, Povey S, Gurling H (1993) 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 18(2):423–425
- 73.
Sunahara RK, Guan HC, O'Dowd BF, Seeman P, Laurier LG, Ng G, George SR, Torchia J, Van Tol HH, Niznik HB (1991) Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature 350(6319):614–619
- 74.
Beischlag TV, Marchese A, Meador-Woodruff JH, Damask SP, O'Dowd BF, Tyndale RF, van Tol HH, Seeman P, Niznik HB (1995) The human dopamine D5 receptor gene: cloning and characterization of the 5′-flanking and promoter region. Biochemistry 34(17):5960–5970
- 75.
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(2):125–145
- 76.
Liu F, Wan Q, Pristupa ZB, Yu XM, Wang YT, Niznik HB (2000) Direct protein–protein coupling enables cross-talk between dopamine D5 and gamma-aminobutyric acid A receptors. Nature 403(6767):274–280
- 77.
Karlsson RM, Hefner KR, Sibley DR, Holmes A (2008) Comparison of dopamine D1 and D5 receptor knockout mice for cocaine locomotor sensitization. Psychopharmacology (Berl) 200(1):117–127
- 78.
Rivkees SA, Lachowicz JE (1997) Functional D1 and D5 dopamine receptors are expressed in the suprachiasmatic, supraoptic, and paraventricular nuclei of primates. Synapse 26(1):1–10
- 79.
Apostolakis EM, Garai J, Clark JH, O'Malley BW (1996) In vivo regulation of central nervous system progesterone receptors: cocaine induces steroid-dependent behavior through dopamine transporter modulation of D5 receptors in rats. Mol Endocrinol 10(12):1595–1604
- 80.
Niznik HBSK (2000) D1-like dopamine receptors: molecular biology and pharmacolgy. Springer Verlag, Di Chiara
- 81.
Sibley DR (1999) New insights into dopaminergic receptor function using antisense and genetically altered animals. Annu Rev Pharmacol Toxicol 39:313–341
- 82.
Kirley A, Hawi Z, Daly G, McCarron M, Mullins C, Millar N, Waldman I, Fitzgerald M, Gill M (2002) Dopaminergic system genes in ADHD: toward a biological hypothesis. Neuropsychopharmacology 27(4):607–619
- 83.
Bakker SC, van der Meulen EM, Oteman N, Schelleman H, Pearson PL, Buitelaar JK, Sinke RJ (2005) DAT1, DRD4, and DRD5 polymorphisms are not associated with ADHD in Dutch families. Am J Med Genet B Neuropsychiatr Genet 132B(1):50–52
- 84.
Barr CL, Wigg KG, Feng Y, Zai G, Malone M, Roberts W, Schachar R, Tannock R, Kennedy JL et al (2000) Attention-deficit hyperactivity disorder and the gene for the dopamine D5 receptor. Mol Psychiatry 5(5):548
- 85.
Hawi Z, Lowe N, Kirley A, Gruenhage F, Nothen M, Greenwood T, Kelsoe J, Fitzgerald M, Gill M (2003) Linkage disequilibrium mapping at DAT1, DRD5 and DBH narrows the search for ADHD susceptibility alleles at these loci. Mol Psychiatry 8(3):299–308
- 86.
Hawi Z, Segurado R, Conroy J, Sheehan K, Lowe N, Kirley A, Shields D, Fitzgerald M, Gallagher L, Gill M (2005) Preferential transmission of paternal alleles at risk genes in attention-deficit/hyperactivity disorder. Am J Hum Genet 77(6):958–965
- 87.
Manor I, Corbex M, Eisenberg J, Gritsenkso I, Bachner-Melman R, Tyano S, Ebstein RP (2004) Association of the dopamine D5 receptor with attention deficit hyperactivity disorder (ADHD) and scores on a continuous performance test (TOVA). Am J Med Genet B Neuropsychiatr Genet 127B(1):73–77
- 88.
Mill J, Curran S, Richards S, Taylor E, Asherson P (2004) Polymorphisms in the dopamine D5 receptor (DRD5) gene and ADHD. Am J Med Genet B Neuropsychiatr Genet 125B(1):38–42
- 89.
Payton A, Holmes J, Barrett JH, Hever T, Fitzpatrick H, Trumper AL, Harrington R, McGuffin P, O'Donovan M, Owen M, Ollier W, Worthington J, Thapar A (2001) Examining for association between candidate gene polymorphisms in the dopamine pathway and attention-deficit hyperactivity disorder: a family-based study. Am J Med Genet 105(5):464–470
- 90.
Langley K, Fowler TA, Grady DL, Moyzis RK, Holmans PA, van den Bree MB, Owen MJ, O'Donovan MC, Thapar A (2009) Molecular genetic contribution to the developmental course of attention-deficit hyperactivity disorder. Eur Child Adolesc Psychiatry 18(1):26–32
- 91.
Kim BN, Kang D, Cho SC, Park TW, Lim MH, Chung YC, Kim JW, Hwang JW, Yoo HJ, Chung US, Son JW, Yang JC, Chung SK, Lee JY, Jung YW (2009) Shorter dinucleotide repeat length in the DRD5 gene is associated with attention deficit hyperactivity disorder. Psychiatr Genet 19(1):57
- 92.
Tahir E, Yazgan Y, Cirakoglu B, Ozbay F, Waldman I, Asherson PJ (2000) Association and linkage of DRD4 and DRD5 with attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children. Mol Psychiatry 5(4):396–404
- 93.
Maher BS, Marazita ML, Ferrell RE, Vanyukov MM (2002) Dopamine system genes and attention deficit hyperactivity disorder: a meta-analysis. Psychiatr Genet 12(4):207–215
- 94.
Kustanovich V, Ishii J, Crawford L, Yang M, McGough JJ, McCracken JT, Smalley SL, Nelson SF (2004) Transmission disequilibrium testing of dopamine-related candidate gene polymorphisms in ADHD: confirmation of association of ADHD with DRD4 and DRD5. Mol Psychiatry 9(7):711–717
- 95.
Vanyukov MM, Moss HB, Yu LM, Deka R (1995) A dinucleotide repeat polymorphism at the gene for monoamine oxidase A and measures of aggressiveness. Psychiatry Res 59(1–2):35–41
- 96.
Eubanks JH, Djabali M, Selleri L, Grandy DK, Civelli O, McElligott DL, Evans GA (1992) Structure and linkage of the D2 dopamine receptor and neural cell adhesion molecule genes on human chromosome 11q23. Genomics 14(4):1010–1018
- 97.
Beaulieu JM, Gainetdinov RR (2011) The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev 63(1):182–217
- 98.
Kamiya T, Saitoh O, Yoshioka K, Nakata H (2003) Oligomerization of adenosine A2A and dopamine D2 receptors in living cells. Biochem Biophys Res Commun 306(2):544–549
- 99.
Binda AV, Kabbani N, Lin R, Levenson R (2002) D2 and D3 dopamine receptor cell surface localization mediated by interaction with protein 4.1 N. Mol Pharmacol 62(3):507–513
- 100.
Smith FD, Oxford GS, Milgram SL (1999) Association of the D2 dopamine receptor third cytoplasmic loop with spinophilin, a protein phosphatase-1-interacting protein. J Biol Chem 274(28):19894–19900
- 101.
Kabbani N, Negyessy L, Lin R, Goldman-Rakic P, Levenson R (2002) Interaction with neuronal calcium sensor NCS-1 mediates desensitization of the D2 dopamine receptor. J Neurosci 22(19):8476–8486
- 102.
Boyson SJ, McGonigle P, Molinoff PB (1986) Quantitative autoradiographic localization of the D1 and D2 subtypes of dopamine receptors in rat brain. J Neurosci 6(11):3177–3188
- 103.
Meador-Woodruff JH, Mansour A, Bunzow JR, Van Tol HH, Watson SJ, Civelli O (1989) Distribution of D2 dopamine receptor mRNA in rat brain. Proc Natl Acad Sci USA 86(19):7625–7628
- 104.
Weiner DM, Brann MR (1989) The distribution of a dopamine D2 receptor mRNA in rat brain. FEBS Lett 253(1–2):207–213
- 105.
Negyessy L, Goldman-Rakic PS (2005) Subcellular localization of the dopamine D2 receptor and coexistence with the calcium-binding protein neuronal calcium sensor-1 in the primate prefrontal cortex. J Comp Neurol 488(4):464–475
- 106.
Doi M, Yujnovsky I, Hirayama J, Malerba M, Tirotta E, Sassone-Corsi P, Borrelli E (2006) Impaired light masking in dopamine D2 receptor-null mice. Nat Neurosci 9(6):732–734
- 107.
Usiello A, Baik JH, Rouge-Pont F, Picetti R, Dierich A, LeMeur M, Piazza PV, Borrelli E (2000) Distinct functions of the two isoforms of dopamine D2 receptors. Nature 408(6809):199–203
- 108.
Heber D, Carpenter CL (2011) Addictive genes and the relationship to obesity and inflammation. Mol Neurobiol 44(2):160–165
- 109.
Tinsley RB, Bye CR, Parish CL, Tziotis-Vais A, George S, Culvenor JG, Li QX, Masters CL, Finkelstein DI, Horne MK (2009) Dopamine D2 receptor knockout mice develop features of Parkinson disease. Ann Neurol 66(4):472–484
- 110.
Glickstein SB, Schmauss C (2001) Dopamine receptor functions: lessons from knockout mice [corrected]. Pharmacol Ther 91(1):63–83
- 111.
Maldonado R, Saiardi A, Valverde O, Samad TA, Roques BP, Borrelli E (1997) Absence of opiate rewarding effects in mice lacking dopamine D2 receptors. Nature 388(6642):586–589
- 112.
Comings DE (1997) IBC's international conference on dopaminergic disorders novel approaches for drug discovery and development. The Ritz-Carlton, Boston
- 113.
Blum K, Sheridan PJ, Wood RC, Braverman ER, Chen TJ, Comings DE (1995) Dopamine D2 receptor gene variants: association and linkage studies in impulsive–addictive–compulsive behaviour. Pharmacogenetics 5(3):121–141
- 114.
Ponce G, Hoenicka J, Rodriguez-Jimenez R, Gozalo A, Jimenez M, Monasor R, Aragues M, Rubio G, Jimenez-Arriero MA, Ramos JA, Palomo T (2004) IDRD2 TaqIA polymorphism is associated with urinary homovanillic acid levels in a sample of Spanish male alcoholic patients. Neurotox Res 6(5):373–377
- 115.
Laakso A, Pohjalainen T, Bergman J, Kajander J, Haaparanta M, Solin O, Syvalahti E, Hietala J (2005) The A1 allele of the human D2 dopamine receptor gene is associated with increased activity of striatal L-amino acid decarboxylase in healthy subjects. Pharmacogenet Genomics 15(6):387–391
- 116.
Thompson J, Thomas N, Singleton A, Piggott M, Lloyd S, Perry EK, Morris CM, Perry RH, Ferrier IN, Court JA (1997) D2 dopamine receptor gene (DRD2) Taq1 A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele. Pharmacogenetics 7(6):479–484
- 117.
Park PS, Kim DK, Jung CH (2008) Dopamine transporter gene and dopamine D2, D3, D4 receptor gene polymorphisms in attention deficit hyperactivity disorder. J Kor Acad Child Adolesc Psychiatry 19(1):19–27
- 118.
Paclt I, Drtilkova I, Kopeckova M, Theiner P, Sery O, Cermakova N (2010) The association between TaqI A polymorphism of ANKK1 (DRD2) gene and ADHD in the Czech boys aged between 6 and 13 years. Neuro Endocrinol Lett 31(1):131–136
- 119.
Kopeckova M, Paclt I, Petrasek J, Pacltova D, Malikova M, Zagatova V (2008) Some ADHD polymorphisms (in genes DAT1, DRD2, DRD3, DBH, 5-HTT) in case–control study of 100 subjects 6–10 age. Neuro Endocrinol Lett 29(2):246–251
- 120.
Qian Q, Wang Y, Li J, Yang L, Wang B, Zhou R, Glatt SJ, Faraone SV (2007) Evaluation of potential gene–gene interactions for attention deficit hyperactivity disorder in the Han Chinese population. Am J Med Genet B Neuropsychiatr Genet 144B(2):200–206
- 121.
Sery O, Drt I, Lkov AI, Theiner P, Pitelov AR, Staif R, Znojil V, Lochman J, Didden W (2006) Polymorphism of DRD2 gene and ADHD. Neuro Endocrinol Lett 27(1–2):236–240
- 122.
Huang YS, Lin SK, Wu YY, Chao CC, Chen CK (2003) A family-based association study of attention-deficit hyperactivity disorder and dopamine D2 receptor TaqI A alleles. Chang Gung Med J 26(12):897–903
- 123.
Rowe DC, Van den Oord EJ, Stever C, Giedinghagen LN, Gard JM, Cleveland HH, Gilson M, Terris ST, Mohr JH, Sherman S, Abramowitz A, Waldman ID (1999) The DRD2 TaqI polymorphism and symptoms of attention deficit hyperactivity disorder. Mol Psychiatry 4(6):580–586
- 124.
Le Coniat M, Sokoloff P, Hillion J, Martres MP, Giros B, Pilon C, Schwartz JC, Berger R (1991) Chromosomal localization of the human D3 dopamine receptor gene. Hum Genet 87(5):618–620
- 125.
Ricci A, Vega JA, Mammola CL, Amenta F (1995) Localisation of dopamine D3 receptor in the rat cerebellar cortex: a light microscope autoradiographic study. Neurosci Lett 190(3):163–166
- 126.
Meador-Woodruff JH, Damask SP, Wang J, Haroutunian V, Davis KL, Watson SJ (1996) Dopamine receptor mRNA expression in human striatum and neocortex. Neuropsychopharmacology 15(1):17–29
- 127.
Shafer RA, Levant B (1998) The D3 dopamine receptor in cellular and organismal function. Psychopharmacology (Berl) 135(1):1–16
- 128.
Kuzhikandathil EV, Oxford GS (1999) Activation of human D3 dopamine receptor inhibits P/Q-type calcium channels and secretory activity in AtT-20 cells. J Neurosci 19(5):1698–1707
- 129.
Cussac D, Newman-Tancredi A, Pasteau V, Millan MJ (1999) Human dopamine D(3) receptors mediate mitogen-activated protein kinase activation via a phosphatidylinositol 3-kinase and an atypical protein kinase C-dependent mechanism. Mol Pharmacol 56(5):1025–1030
- 130.
Fields RD, Eshete F, Stevens B, Itoh K (1997) Action potential-dependent regulation of gene expression: temporal specificity in ca2+, cAMP-responsive element binding proteins, and mitogen-activated protein kinase signaling. J Neurosci 17(19):7252–7266
- 131.
Cho DI, Oak MH, Yang HJ, Choi HK, Janssen GM, Kim KM (2003) Direct and biochemical interaction between dopamine D3 receptor and elongation factor-1Bbetagamma. Life Sci 73(23):2991–3004
- 132.
Black KJ, Hershey T, Koller JM, Videen TO, Mintun MA, Price JL, Perlmutter JS (2002) A possible substrate for dopamine-related changes in mood and behavior: prefrontal and limbic effects of a D3-preferring dopamine agonist. Proc Natl Acad Sci USA 99(26):17113–17118
- 133.
Beninger RJ, Banasikowski TJ (2008) Dopaminergic mechanism of reward-related incentive learning: focus on the dopamine D(3) receptor. Neurotox Res 14(1):57–70
- 134.
Lane HY, Liu YC, Huang CL, Hsieh CL, Chang YL, Chang L, Chang YC, Chang WH (2008) Prefrontal executive function and D1, D3, 5-HT2A and 5-HT6 receptor gene variations in healthy adults. J Psychiatry Neurosci 33(1):47–53
- 135.
Limosin F, Romo L, Batel P, Ades J, Boni C, Gorwood P (2005) Association between dopamine receptor D3 gene BalI polymorphism and cognitive impulsiveness in alcohol-dependent men. Eur Psychiatry 20(3):304–306
- 136.
Muglia P, Jain U, Kennedy JL (2002) A transmission disequilibrium test of the Ser9/Gly dopamine D3 receptor gene polymorphism in adult attention-deficit hyperactivity disorder. Behav Brain Res 130(1–2):91–95
- 137.
Barr CL, Wigg KG, Wu J, Zai C, Bloom S, Tannock R, Roberts W, Malone M, Schachar R, Kennedy JL (2000) Linkage study of two polymorphisms at the dopamine D3 receptor gene and attention-deficit hyperactivity disorder. Am J Med Genet 96(1):114–117
- 138.
Guan L, Wang B, Chen Y, Yang L, Li J, Qian Q, Wang Z, Faraone SV, Wang Y (2009) A high-density single-nucleotide polymorphism screen of 23 candidate genes in attention deficit hyperactivity disorder: suggesting multiple susceptibility genes among Chinese Han population. Mol Psychiatry 14(5):546–554
- 139.
Davis C, Patte K, Levitan RD, Carter J, Kaplan AS, Zai C, Reid C, Curtis C, Kennedy JL (2009) A psycho-genetic study of associations between the symptoms of binge eating disorder and those of attention deficit (hyperactivity) disorder. J Psychiatr Res 43(7):687–696
- 140.
Brookes K, Xu X, Chen W, Zhou K, Neale B, Lowe N, Anney R, Franke B, Gill M, Ebstein R, Buitelaar J, Sham P, Campbell D, Knight J, Andreou P, Altink M, Arnold R, Boer F, Buschgens C, Butler L, Christiansen H, Feldman L, Fleischman K, Fliers E, Howe-Forbes R, Goldfarb A, Heise A, Gabriels I, Korn-Lubetzki I, Johansson L, Marco R, Medad S, Minderaa R, Mulas F, Muller U, Mulligan A, Rabin K, Rommelse N, Sethna V, Sorohan J, Uebel H, Psychogiou L, Weeks A, Barrett R, Craig I, Banaschewski T, Sonuga-Barke E, Eisenberg J, Kuntsi J, Manor I, McGuffin P, Miranda A, Oades RD, Plomin R, Roeyers H, Rothenberger A, Sergeant J, Steinhausen HC, Taylor E, Thompson M, Faraone SV, Asherson P (2006) The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes. Mol Psychiatry 11(10):934–953
- 141.
Petronis A, Van Tol HH, Lichter JB, Livak KJ, Kennedy JL (1993) The D4 dopamine receptor gene maps on 11p proximal to HRAS. Genomics 18(1):161–163
- 142.
Gelernter J, Kennedy JL, van Tol HH, Civelli O, Kidd KK (1992) The D4 dopamine receptor (DRD4) maps to distal 11p close to HRAS. Genomics 13(1):208–210
- 143.
Defagot MC, Malchiodi EL, Villar MJ, Antonelli MC (1997) Distribution of D4 dopamine receptor in rat brain with sequence-specific antibodies. Brain Res Mol Brain Res 45(1):1–12
- 144.
Wedzony K, Chocyk A, Mackowiak M, Fijal K, Czyrak A (2000) Cortical localization of dopamine D4 receptors in the rat brain—immunocytochemical study. J Physiol Pharmacol 51(2):205–221
- 145.
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(2):219–229
- 146.
Deth R, Muratore C, Benzecry J, Power-Charnitsky VA, Waly M (2008) How environmental and genetic factors combine to cause autism: a redox/methylation hypothesis. Neurotoxicology 29(1):190–201
- 147.
Kuznetsova AY, Deth RC (2008) A model for modulation of neuronal synchronization by D4 dopamine receptor-mediated phospholipid methylation. J Comput Neurosci 24(3):314–329
- 148.
Dulawa SC, Grandy DK, Low MJ, Paulus MP, Geyer MA (1999) Dopamine D4 receptor-knock-out mice exhibit reduced exploration of novel stimuli. J Neurosci 19(21):9550–9556
- 149.
Rubinstein M, Phillips TJ, Bunzow JR, Falzone TL, Dziewczapolski G, Zhang G, Fang Y, Larson JL, McDougall JA, Chester JA, Saez C, Pugsley TA, Gershanik O, Low MJ, Grandy DK (1997) Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine. Cell 90(6):991–1001
- 150.
Das M, Das BA, Bhaduri N, Sarkar K, Ghosh P, Sinha S, Ray A, Chatterjee A, Mukhopadhyay K (2011) Role of gene–gene/gene–environment interaction in the etiology of eastern Indian ADHD probands. Prog Neuropsychopharmacol Biol Psychiatry 35(2):577–587
- 151.
Gabriela ML, John DG, Magdalena BV, Ariadna GS, Francisco DL, Liz SM, Lino PC, Josefina RG, Ernesto RZ, Carlos CF (2009) Genetic interaction analysis for DRD4 and DAT1 genes in a group of Mexican ADHD patients. Neurosci Lett 451(3):257–260
- 152.
Niederhofer H, Menzel F, Gobel K, Hackenberg B, Richter R, Walter MH, Gross C, Huber M, Pycha R, Menzel HJ (2008) A preliminary report of the dopamine receptor D(4) and the dopamine transporter 1 gene polymorphism and its association with attention deficit hyperactivity disorder. Neuropsychiatr Dis Treat 4(4):701–705
- 153.
Johnson KA, Kelly SP, Robertson IH, Barry E, Mulligan A, Daly M, Lambert D, McDonnell C, Connor TJ, Hawi Z, Gill M, Bellgrove MA (2008) Absence of the 7-repeat variant of the DRD4 VNTR is associated with drifting sustained attention in children with ADHD but not in controls. Am J Med Genet B Neuropsychiatr Genet 147B(6):927–937
- 154.
Gornick MC, Addington A, Shaw P, Bobb AJ, Sharp W, Greenstein D, Arepalli S, Castellanos FX, Rapoport JL (2007) Association of the dopamine receptor D4 (DRD4) gene 7-repeat allele with children with attention-deficit/hyperactivity disorder (ADHD): an update. Am J Med Genet B Neuropsychiatr Genet 144(3):379–382
- 155.
Cheuk DK, Li SY, Wong V (2006) Exon 3 polymorphisms of dopamine D4 receptor (DRD4) gene and attention deficit hyperactivity disorder in Chinese children. Am J Med Genet B Neuropsychiatr Genet 141B(8):907–911
- 156.
Leung PW, Lee CC, Hung SF, Ho TP, Tang CP, Kwong SL, Leung SY, Yuen ST, Lieh-Mak F, Oosterlaan J, Grady D, Harxhi A, Ding YC, Chi HC, Flodman P, Schuck S, Spence MA, Moyzis R, Swanson J (2005) Dopamine receptor D4 (DRD4) gene in Han Chinese children with attention-deficit/hyperactivity disorder (ADHD): increased prevalence of the 2-repeat allele. Am J Med Genet B Neuropsychiatr Genet 133B(1):54–56
- 157.
Kim YS, Leventhal BL, Kim SJ, Kim BN, Cheon KA, Yoo HJ, Kim SJ, Badner J, Cook EH (2005) Family-based association study of DAT1 and DRD4 polymorphism in Korean children with ADHD. Neurosci Lett 390(3):176–181
- 158.
Brookes KJ, Xu X, Chen CK, Huang YS, Wu YY, Asherson P (2005) No evidence for the association of DRD4 with ADHD in a Taiwanese population within-family study. BMC Med Genet 6:31
- 159.
Qian Q, Wang Y, Zhou R, Yang L, Faraone SV (2004) Family-based and case–control association studies of DRD4 and DAT1 polymorphisms in Chinese attention deficit hyperactivity disorder patients suggest long repeats contribute to genetic risk for the disorder. Am J Med Genet B Neuropsychiatr Genet 128B(1):84–89
- 160.
Arcos-Burgos M, Castellanos FX, Konecki D, Lopera F, Pineda D, Palacio JD, Rapoport JL, Berg K, Bailey-Wilson J, Muenke M (2004) Pedigree disequilibrium test (PDT) replicates association and linkage between DRD4 and ADHD in multigenerational and extended pedigrees from a genetic isolate. Mol Psychiatry 9(3):252–259
- 161.
Smith KM, Daly M, Fischer M, Yiannoutsos CT, Bauer L, Barkley R, Navia BA (2003) Association of the dopamine beta hydroxylase gene with attention deficit hyperactivity disorder: genetic analysis of the Milwaukee longitudinal study. Am J Med Genet B Neuropsychiatr Genet 119B(1):77–85
- 162.
Holmes J, Payton A, Barrett J, Harrington R, McGuffin P, Owen M, Ollier W, Worthington J, Gill M, Kirley A, Hawi Z, Fitzgerald M, Asherson P, Curran S, Mill J, Gould A, Taylor E, Kent L, Craddock N, Thapar A (2002) Association of DRD4 in children with ADHD and comorbid conduct problems. Am J Med Genet 114(2):150–153
- 163.
Mill J, Curran S, Kent L, Richards S, Gould A, Virdee V, Huckett L, Sharp J, Batten C, Fernando S, Simanoff E, Thompson M, Zhao J, Sham P, Taylor E, Asherson P (2001) Attention deficit hyperactivity disorder (ADHD) and the dopamine D4 receptor gene: evidence of association but no linkage in a UK sample. Mol Psychiatry 6(4):440–444
- 164.
Todd RD, Neuman RJ, Lobos EA, Jong YJ, Reich W, Heath AC (2001) Lack of association of dopamine D4 receptor gene polymorphisms with ADHD subtypes in a population sample of twins. Am J Med Genet 105(5):432–438
- 165.
Curran S, Mill J, Sham P, Rijsdijk F, Marusic K, Taylor E, Asherson P (2001) QTL association analysis of the DRD4 exon 3 VNTR polymorphism in a population sample of children screened with a parent rating scale for ADHD symptoms. Am J Med Genet 105(4):387–393
- 166.
Roman T, Schmitz M, Polanczyk G, Eizirik M, Rohde LA, Hutz MH (2001) Attention-deficit hyperactivity disorder: a study of association with both the dopamine transporter gene and the dopamine D4 receptor gene. Am J Med Genet 105(5):471–478
- 167.
Kotler M, Manor I, Sever Y, Eisenberg J, Cohen H, Ebstein RP, Tyano S (2000) Failure to replicate an excess of the long dopamine D4 exon III repeat polymorphism in ADHD in a family-based study. Am J Med Genet 96(3):278–281
- 168.
Hawi Z, McCarron M, Kirley A, Daly G, Fitzgerald M, Gill M (2000) No association of the dopamine DRD4 receptor (DRD4) gene polymorphism with attention deficit hyperactivity disorder (ADHD) in the Irish population. Am J Med Genet 96(3):268–272
- 169.
Holmes J, Payton A, Barrett JH, Hever T, Fitzpatrick H, Trumper AL, Harrington R, McGuffin P, Owen M, Ollier W et al (2000) A family-based and case–control association study of the dopamine D4 receptor gene and dopamine transporter gene in attention deficit hyperactivity disorder. Mol Psychiatry 5(5):523
- 170.
Comings DE, Gonzalez N, Wu S, Gade R, Muhleman D, Saucier G, Johnson P, Verde R, Rosenthal RJ, Lesieur HR, Rugle LJ, Miller WB, MacMurray JP (1999) Studies of the 48 bp repeat polymorphism of the DRD4 gene in impulsive, compulsive, addictive behaviors: Tourette syndrome, ADHD, pathological gambling, and substance abuse. Am J Med Genet 88(4):358–368
- 171.
Swanson JM, Sunohara GA, Kennedy JL, Regino R, Fineberg E, Wigal T, Lerner M, Williams L, LaHoste GJ, Wigal S (1998) Association of the dopamine receptor D4 (DRD4) gene with a refined phenotype of attention deficit hyperactivity disorder (ADHD): a family-based approach. Mol Psychiatry 3(1):38–41
- 172.
Rowe DC, Stever C, Giedinghagen LN, Gard J, Cleveland HH, Terris ST, Mohr JH, Sherman S, Abramowitz A, Waldman ID (1998) Dopamine DRD4 receptor polymorphism and attention deficit hyperactivity disorder. Mol Psychiatry 3(5):419–426
- 173.
Sunohara GA, Roberts W, Malone M, Schachar RJ, Tannock R, Basile VS, Wigal T, Wigal SB, Schuck S, Moriarty J, Swanson JM, Kennedy JL, Barr CL (2000) Linkage of the dopamine D4 receptor gene and attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 39(12):1537–1542
- 174.
Reiersen AM, Todorov AA (2011) Association between DRD4 genotype and autistic symptoms in DSM-IV ADHD. J Can Acad Child Adolesc Psychiatry 20(1):15
- 175.
Becker K, Blomeyer D, El-Faddagh M, Esser G, Schmidt MH, Banaschewski T, Laucht M (2010) From regulatory problems in infancy to attention-deficit/hyperactivity disorder in childhood: a moderating role for the dopamine D4 receptor gene? J Pediatr 156(5):798–803
- 176.
Kereszturi E, Tarnok Z, Bognar E, Lakatos K, Farkas L, Gadoros J, Sasvari-Szekely M, Nemoda Z (2008) Catechol-O-methyltransferase Val158Met polymorphism is associated with methylphenidate response in ADHD children. Am J Med Genet B Neuropsychiatr Genet 147B(8):1431–1435
- 177.
Carrasco X, Rothhammer P, Moraga M, Henriquez H, Chakraborty R, Aboitiz F, Rothhammer F (2006) Genotypic interaction between DRD4 and DAT1 loci is a high risk factor for attention-deficit/hyperactivity disorder in Chilean families. Am J Med Genet B Neuropsychiatr Genet 141B(1):51–54
- 178.
El-Faddagh M, Laucht M, Maras A, Vohringer L, Schmidt MH (2004) Association of dopamine D4 receptor (DRD4) gene with attention-deficit/hyperactivity disorder (ADHD) in a high-risk community sample: a longitudinal study from birth to 11 years of age. J Neural Transm 111(7):883–889
- 179.
Lowe N, Kirley A, Mullins C, Fitzgerald M, Gill M, Hawi Z (2004) Multiple marker analysis at the promoter region of the DRD4 gene and ADHD: evidence of linkage and association with the SNP -616. Am J Med Genet B Neuropsychiatr Genet 131B(1):33–37
- 180.
Frank Y, Pergolizzi RG, Perilla MJ (2004) Dopamine D4 receptor gene and attention deficit hyperactivity disorder. Pediatr Neurol 31(5):345–348
- 181.
Lunetta KL, Faraone SV, Biederman J, Laird NM (2000) Family-based tests of association and linkage that use unaffected sibs, covariates, and interactions. Am J Hum Genet 66(2):605–614
- 182.
McCracken JT, Smalley SL, McGough JJ, Crawford L, Del Homme M, Cantor RM, Liu A, Nelson SF et al (2000) Evidence for linkage of a tandem duplication polymorphism upstream of the dopamine D4 receptor gene (DRD4) with attention deficit hyperactivity disorder (ADHD). Mol Psychiatry 5(5):531–536
- 183.
Smalley SL, Bailey JN, Palmer CG, Cantwell DP, McGough JJ, Del'Homme MA, Asarnow JR, Woodward JA, Ramsey C, Nelson SF et al (1998) Evidence that the dopamine D4 receptor is a susceptibility gene in attention deficit hyperactivity disorder. Mol Psychiatry 3(5):427
- 184.
LaHoste GJ, Swanson JM, Wigal SB, Glabe C, Wigal T, King N, Kennedy JL (1996) Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder. Mol Psychiatry 1(2):121–124
- 185.
Payton A, Holmes J, Barrett JH, Sham P, Harrington R, McGuffin P, Owen M, Ollier W, Worthington J, Thapar A (2001) Susceptibility genes for a trait measure of attention deficit hyperactivity disorder: a pilot study in a non-clinical sample of twins. Psychiatry Res 105(3):273–278
- 186.
Asghari V, Schoots O, van Kats S, Ohara K, Jovanovic V, Guan HC, Bunzow JR, Petronis A, Van Tol HH (1994) Dopamine D4 receptor repeat: analysis of different native and mutant forms of the human and rat genes. Mol Pharmacol 46(2):364–373
- 187.
Asghari V, Sanyal S, Buchwaldt S, Paterson A, Jovanovic V, Van Tol HH (1995) Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants. J Neurochem 65(3):1157–1165
- 188.
Kotler M, Cohen H, Segman R, Gritsenko I, Nemanov L, Lerer B, Kramer I, Zer-Zion M, Kletz I, Ebstein RP (1997) Excess dopamine D4 receptor (D4DR) exon III seven repeat allele in opioid-dependent subjects. Mol Psychiatry 2(3):251–254
- 189.
Benjamin J, Li L, Patterson C, Greenberg BD, Murphy DL, Hamer DH (1996) Population and familial association between the D4 dopamine receptor gene and measures of Novelty Seeking. Nat Genet 12(1):81–84
- 190.
Bhaduri N, Das M, Sinha S, Chattopadhyay A, Gangopadhyay PK, Chaudhuri K, Singh M, Mukhopadhyay K (2006) Association of dopamine D4 receptor (DRD4) polymorphisms with attention deficit hyperactivity disorder in Indian population. Am J Med Genet B Neuropsychiatr Genet 141B(1):61–66
- 191.
Shaw P, Gornick M, Lerch J, Addington A, Seal J, Greenstein D, Sharp W, Evans A, Giedd JN, Castellanos FX, Rapoport JL (2007) Polymorphisms of the dopamine D4 receptor, clinical outcome, and cortical structure in attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 64(8):921–931
- 192.
Swanson J, Oosterlaan J, Murias M, Schuck S, Flodman P, Spence MA, Wasdell M, Ding Y, Chi HC, Smith M et al (2000) Attention deficit/hyperactivity disorder children with a 7-repeat allele of the dopamine receptor D4 gene have extreme behavior but normal performance on critical neuropsychological tests of attention. Proc Natl Acad Sci 97(9):4754
- 193.
Yang JW, Jang WS, Hong SD, Ji YI, Kim DH, Park J, Kim SW, Joung YS (2008) A case–control association study of the polymorphism at the promoter region of the DRD4 gene in Korean boys with attention deficit-hyperactivity disorder: evidence of association with the -521 C/T SNP. Prog Neuropsychopharmacol Biol Psychiatry 32(1):243–248
- 194.
Kereszturi E, Kiraly O, Csapo Z, Tarnok Z, Gadoros J, Sasvari-Szekely M, Nemoda Z (2007) Association between the 120-bp duplication of the dopamine D4 receptor gene and attention deficit hyperactivity disorder: genetic and molecular analyses. Am J Med Genet B Neuropsychiatr Genet 144B(2):231–236
- 195.
Seaman MI, Fisher JB, Chang F, Kidd KK (1999) Tandem duplication polymorphism upstream of the dopamine D4 receptor gene (DRD4). Am J Med Genet 88(6):705–709
- 196.
Ronai Z, Guttman A, Keszler G, Sasvari-Szekely M (2004) Capillary electrophoresis study on DNA–protein complex formation in the polymorphic 5′ upstream region of the dopamine D4 receptor (DRD4) gene. Curr Med Chem 11(8):1023–1029
- 197.
D'Souza UM, Russ C, Tahir E, Mill J, McGuffin P, Asherson PJ, Craig IW (2004) Functional effects of a tandem duplication polymorphism in the 5′ flanking region of the DRD4 gene. Biol Psychiatry 56(9):691–697
- 198.
Rogers G, Joyce P, Mulder R, Sellman D, Miller A, Allington M, Olds R, Wells E, Kennedy M (2004) Association of a duplicated repeat polymorphism in the 5′-untranslated region of the DRD4 gene with novelty seeking. Am J Med Genet B Neuropsychiatr Genet 126B(1):95–98
- 199.
Barr CL, Feng Y, Wigg KG, Schachar R, Tannock R, Roberts W, Malone M, Kennedy JL (2001) 5′-untranslated region of the dopamine D4 receptor gene and attention-deficit hyperactivity disorder. Am J Med Genet 105(1):84–90
- 200.
Martel MM, Nikolas M, Jernigan K, Friderici K, Nigg JT (2010) Personality mediation of genetic effects on attention-deficit/hyperactivity disorder. J Abnorm Child Psychol 38(5):633–643
- 201.
Szilagyi A, Boor K, Szekely A, Gaszner P, Kalasz H, Sasvari-Szekely M, Barta C (2005) Combined effect of promoter polymorphisms in the dopamine D4 receptor and the serotonin transporter genes in heroin dependence. Neuropsychopharmacol Hung 7(1):28–33
- 202.
Okuyama Y, Ishiguro H, Toru M, Arinami T (1999) A genetic polymorphism in the promoter region of DRD4 associated with expression and schizophrenia. Biochem Biophys Res Commun 258(2):292–295
- 203.
Lakatos K, Nemoda Z, Toth I, Ronai Z, Ney K, Sasvari-Szekely M, Gervai J (2002) Further evidence for the role of the dopamine D4 receptor (DRD4) gene in attachment disorganization: interaction of the exon III 48-bp repeat and the −521 C/T promoter polymorphisms. Mol Psychiatry 7(1):27–31
- 204.
Ronai Z, Szekely A, Nemoda Z, Lakatos K, Gervai J, Staub M, Sasvari-Szekely M (2001) Association between novelty seeking and the −521 C/T polymorphism in the promoter region of the DRD4 gene. Mol Psychiatry 6(1):35–38
- 205.
Guan LL, Wang YF, Li J, Wang B, Yang L, Qian QJ (2007) Association analysis of dopamine D4 receptor gene polymorphism and attention deficit hyperactivity disorder with/without disruptive behavior disorder]. Beijing da xue xue bao. Yi xue ban=. J Peking Univ Health Sci 39(3):233
- 206.
Williams T, Tjian R (1991) Analysis of the DNA-binding and activation properties of the human transcription factor AP-2. Genes Dev 5(4):670–682
- 207.
Imagawa M, Chiu R, Karin M (1987) Transcription factor AP-2 mediates induction by two different signal-transduction pathways: protein kinase C and cAMP. Cell 51(2):251–260
- 208.
Wu F, Lee AS (1998) Identification of AP-2 as an interactive target of Rb and a regulator of the G1/S control element of the hamster histone H3.2 promoter. Nucleic Acids Res 26(21):4837–4845
- 209.
Ronai Z, Szantai E, Szmola R, Nemoda Z, Szekely A, Gervai J, Guttman A, Sasvari-Szekely M (2004) A novel A/G SNP in the −615th position of the dopamine D4 receptor promoter region as a source of misgenotyping of the −616 C/G SNP. Am J Med Genet B Neuropsychiatr Genet 126B(1):74–78
- 210.
Catalano M, Nobile M, Novelli E, Nothen MM, Smeraldi E (1993) Distribution of a novel mutation in the first exon of the human dopamine D4 receptor gene in psychotic patients. Biol Psychiatry 34(7):459–464
- 211.
Barr CL, Wigg KG, Bloom S, Schachar R, Tannock R, Roberts W, Malone M, Kennedy JL (2000) Further evidence from haplotype analysis for linkage of the dopamine D4 receptor gene and attention-deficit hyperactivity disorder. Am J Med Genet 96(3):262–267
- 212.
Hong CJ, Chiu HJ, Chang YS, Sim CB (1998) Twelve-nucleotide repeat polymorphism of D4 dopamine receptor gene in Chinese familial schizophrenic patients. Biol Psychiatry 43(6):432–435
- 213.
Uh M, White BH, Sidhu A (1998) Alteration of association of agonist-activated renal D1(A) dopamine receptors with G proteins in proximal tubules of the spontaneously hypertensive rat. J Hypertens 16(9):1307–1313
- 214.
Kimura K, White BH, Sidhu A (1995) Coupling of human D-1 dopamine receptors to different guanine nucleotide binding proteins. Evidence that D-1 dopamine receptors can couple to both Gs and G(o). J Biol Chem 270(24):14672–14678
- 215.
Sidhu A (1998) Coupling of D1 and D5 dopamine receptors to multiple G proteins: implications for understanding the diversity in receptor-G protein coupling. Mol Neurobiol 16(2):125–134
- 216.
Sidhu A, Kimura K, Uh M, White BH, Patel S (1998) Multiple coupling of human D5 dopamine receptors to guanine nucleotide binding proteins Gs and Gz. J Neurochem 70(6):2459–2467
- 217.
Obadiah J, Avidor-Reiss T, Fishburn CS, Carmon S, Bayewitch M, Vogel Z, Fuchs S, Levavi-Sivan B (1999) Adenylyl cyclase interaction with the D2 dopamine receptor family; differential coupling to Gi, Gz, and Gs. Cell Mol Neurobiol 19(5):653–664
- 218.
Wolfe SE, Morris SJ (1999) Dopamine D2 receptor isoforms expressed in AtT20 cells differentially couple to G proteins to acutely inhibit high voltage-activated calcium channels. J Neurochem 73(6):2375–2382
- 219.
Watts VJ, Wiens BL, Cumbay MG, Vu MN, Neve RL, Neve KA (1998) Selective activation of Galphao by D2L dopamine receptors in NS20Y neuroblastoma cells. J Neurosci 18(21):8692–8699
- 220.
Grunewald S, Reilander H, Michel H (1996) In vivo reconstitution of dopamine D2S receptor-mediated G protein activation in baculovirus-infected insect cells: preferred coupling to Gi1 versus Gi2. Biochemistry 35(48):15162–15173
- 221.
O'Hara CM, Tang L, Taussig R, Todd RD, O'Malley KL (1996) Dopamine D2L receptor couples to G alpha i2 and G alpha i3 but not G alpha i1, leading to the inhibition of adenylate cyclase in transfected cell lines. J Pharmacol Exp Ther 278(1):354–360
- 222.
Newman-Tancredi A, Cussac D, Audinot V, Pasteau V, Gavaudan S, Millan MJ (1999) G protein activation by human dopamine D3 receptors in high-expressing Chinese hamster ovary cells: A guanosine-5′-O-(3-[35S]thio)-triphosphate binding and antibody study. Mol Pharmacol 55(3):564–574
- 223.
Robinson SW, Caron MG (1997) Selective inhibition of adenylyl cyclase type V by the dopamine D3 receptor. Mol Pharmacol 52(3):508–514
- 224.
Levy F (1991) The dopamine theory of attention deficit hyperactivity disorder (ADHD). Aust N Z J Psychiatry 25(2):277–283
- 225.
Yamaguchi I, Harmon SK, Todd RD, O'Malley KL (1997) The rat D4 dopamine receptor couples to cone transducin (Galphat2) to inhibit forskolin-stimulated cAMP accumulation. J Biol Chem 272(26):16599–16602
- 226.
Oldenhof J, Vickery R, Anafi M, Oak J, Ray A, Schoots O, Pawson T, von Zastrow M, Van Tol HH (1998) SH3 binding domains in the dopamine D4 receptor. Biochemistry 37(45):15726–15736
Acknowledgments
The manuscript is supported by the National Nature Science Foundation of China (NSFC) (81101016), New Century Excellent Talents in University (NCET-10-0421), and the Ministry of Science and Technology of China (2011DFG33250).
Conflicts of interest
The authors declared no conflicts of interest.
Author information
Affiliations
Corresponding author
Electronic Supplementary Material
Below is the link to the electronic supplementary material.
ESM 1
(DOC 471 kb)
Rights and permissions
About this article
Cite this article
Wu, J., Xiao, H., Sun, H. et al. Role of Dopamine Receptors in ADHD: A Systematic Meta-analysis. Mol Neurobiol 45, 605–620 (2012). https://doi.org/10.1007/s12035-012-8278-5
Received:
Accepted:
Published:
Issue Date:
Keywords
- ADHD
- Dopamine receptor
- Meta-analysis