dopamine d4 receptors


Summary: A subtype of dopamine D2 receptors that has high affinity for the antipsychotic CLOZAPINE.

Top Publications

  1. Durston S, de Zeeuw P, Staal W. Imaging genetics in ADHD: a focus on cognitive control. Neurosci Biobehav Rev. 2009;33:674-89 pubmed publisher
    ..Other avenues of investigation are suggested by a combination of data- and theory-driven approaches in both genetics and neuroimaging. ..
  2. Michaelides M, Pascau J, Gispert J, Delis F, Grandy D, Wang G, et al. Dopamine D4 receptors modulate brain metabolic activity in the prefrontal cortex and cerebellum at rest and in response to methylphenidate. Eur J Neurosci. 2010;32:668-76 pubmed publisher
    ..Here we examined the contribution of dopamine D4 receptors (D4Rs) to baseline brain glucose metabolism and to the regional metabolic responses to MP...
  3. Jackson C, Chaurasia S, Zhou H, Haque R, Storm D, Iuvone P. Essential roles of dopamine D4 receptors and the type 1 adenylyl cyclase in photic control of cyclic AMP in photoreceptor cells. J Neurochem. 2009;109:148-57 pubmed publisher
    ..These observations illustrate a novel mechanism for cross-talk between dopamine and photic signaling pathways regulating cyclic AMP in photoreceptor cells. ..
  4. Graziane N, Yuen E, Yan Z. Dopamine D4 Receptors Regulate GABAA Receptor Trafficking via an Actin/Cofilin/Myosin-dependent Mechanism. J Biol Chem. 2009;284:8329-36 pubmed publisher
  5. Marco Pallares J, Cucurell D, Cunillera T, Krämer U, Camara E, Nager W, et al. Genetic variability in the dopamine system (dopamine receptor D4, catechol-O-methyltransferase) modulates neurophysiological responses to gains and losses. Biol Psychiatry. 2009;66:154-61 pubmed publisher
    ..In addition, the present results might agree with the phasic/tonic dopamine theory that predicts higher phasic dopamine responses in ValVal participants. ..
  6. Thanos P, Bermeo C, Rubinstein M, Suchland K, Wang G, Grandy D, et al. Conditioned place preference and locomotor activity in response to methylphenidate, amphetamine and cocaine in mice lacking dopamine D4 receptors. J Psychopharmacol. 2010;24:897-904 pubmed publisher
    ..Thus, individuals with D4 receptor polymorphisms might show enhanced reinforcing responses to MP and AMPH and attenuated locomotor response to AMPH. ..
  7. Nemirovsky S, Avale M, Brunner D, Rubinstein M. Reward-seeking and discrimination deficits displayed by hypodopaminergic mice are prevented in mice lacking dopamine D4 receptors. Synapse. 2009;63:991-7 pubmed publisher
    ..In summary, hypodopaminergic mice exhibit severe impairments to retrieve rewards in two operant positive reinforcement tasks, but these deleterious effects are totally prevented in the absence of functional D4Rs. ..
  8. Cummings D, Ericksen S, Goetz A, Schetz J. Transmembrane segment five serines of the D4 dopamine receptor uniquely influence the interactions of dopamine, norepinephrine, and Ro10-4548. J Pharmacol Exp Ther. 2010;333:682-95 pubmed publisher
  9. Smith T. Meta-analysis of the heterogeneity in association of DRD4 7-repeat allele and AD/HD: stronger association with AD/HD combined type. Am J Med Genet B Neuropsychiatr Genet. 2010;153B:1189-99 pubmed publisher
    ..Implications regarding AD/HD etiological and phenotypic heterogeneity are discussed. ..

More Information


  1. Biederman J, Petty C, Ten Haagen K, Small J, Doyle A, Spencer T, et al. Effect of candidate gene polymorphisms on the course of attention deficit hyperactivity disorder. Psychiatry Res. 2009;170:199-203 pubmed publisher
    ..94) and 5HTTLPR long allele. Our findings suggest that the DRD4 7-repeat allele is associated with a more persistent course of ADHD. ..
  2. Eisenberg D, Apicella C, Campbell B, Dreber A, Garcia J, Lum J. Assortative human pair-bonding for partner ancestry and allelic variation of the dopamine receptor D4 (DRD4) gene. Soc Cogn Affect Neurosci. 2010;5:194-202 pubmed publisher
    ..However, replications and extensions of this study are needed and the way ancestry/race is assessed must be carefully considered. ..
  3. Bos Veneman N, Minderaa R, Hoekstra P. The DRD4 gene and severity of tics and comorbid symptoms: main effects and interactions with delivery complications. Mov Disord. 2010;25:1470-6 pubmed publisher
  4. Perkins K. Acute responses to nicotine and smoking: implications for prevention and treatment of smoking in lower SES women. Drug Alcohol Depend. 2009;104 Suppl 1:S79-86 pubmed publisher
  5. Reiner I, Spangler G. Adult attachment and gene polymorphisms of the dopamine D4 receptor and serotonin transporter (5-HTT). Attach Hum Dev. 2010;12:209-29 pubmed publisher
    ..These findings encourage further investigations to explore endophenotypical and mediating psychological processes between the DRD4 Gene and secure attachment patterns. ..
  6. Kebir O, Grizenko N, Sengupta S, Joober R. Verbal but not performance IQ is highly correlated to externalizing behavior in boys with ADHD carrying both DRD4 and DAT1 risk genotypes. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:939-44 pubmed publisher
    ..Further investigations are required to replicate these results and determine specificity to ADHD. ..
  7. Cummings D, Ericksen S, Schetz J. Three amino acids in the D2 dopamine receptor regulate selective ligand function and affinity. J Neurochem. 2009;110:45-57 pubmed publisher
    ..Consistent with the experimental data, this model illustrates the interactions between a variety of subtype-selective ligands and the wild-type D(2), mutant D(2), or wild-type D(4) receptors. ..
  8. Schmidt L, Fox N, Perez Edgar K, Hamer D. Linking gene, brain, and behavior: DRD4, frontal asymmetry, and temperament. Psychol Sci. 2009;20:831-7 pubmed publisher
    ..We discuss how the interaction of genetic and endoenvironmental factors may confer risk and protection for different behavioral styles in children. ..
  9. Simpson J, Vetuz G, Wilson M, Brookes K, Kent L. 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. 2010;153B:1228-33 pubmed publisher
    ..Employing post-mortem brain tissue, rather than using in vitro techniques may provide a more relevant paradigm to study functional effects of reported risk alleles. ..
  10. Gervai J, Novak A, Lakatos K, Toth I, Danis I, Ronai Z, et al. Infant genotype may moderate sensitivity to maternal affective communications: attachment disorganization, quality of care, and the DRD4 polymorphism. Soc Neurosci. 2007;2:307-19 pubmed publisher
    ..Among carriers of the 7-repeat DRD4 allele, there was no relation between quality of maternal communication and infant disorganization. This interaction effect was independent of degree of social risk and maternal DRD4 genotype. ..
  11. Hattori E, Nakajima M, Yamada K, Iwayama Y, Toyota T, Saitou N, et al. Variable number of tandem repeat polymorphisms of DRD4: re-evaluation of selection hypothesis and analysis of association with schizophrenia. Eur J Hum Genet. 2009;17:793-801 pubmed publisher
    ..Collectively, this study suggests that the VNTR variation does not have an effect large enough to cause either selection or a detectable association with schizophrenia in a study of samples of moderate size. ..
  12. Cardo E, Nevot A, Redondo M, Melero A, de Azua B, García De la Banda G, et al. [Attention deficit disorder and hyperactivity: a pattern of evolution?]. Rev Neurol. 2010;50 Suppl 3:S143-7 pubmed
    ..It is possible that the presence of altered gene combinations, as in ADHD, can bring concrete benefits to society but are detrimental to the individual. ..
  13. Rondou P, Haegeman G, Van Craenenbroeck K. The dopamine D4 receptor: biochemical and signalling properties. Cell Mol Life Sci. 2010;67:1971-86 pubmed publisher
    ..We provide an overview of the structure, signalling properties and regulation of dopamine D4 receptors, and briefly discuss their physiological and pathophysiological role in the brain.
  14. Feldstein Ewing S, LaChance H, Bryan A, Hutchison K. Do genetic and individual risk factors moderate the efficacy of motivational enhancement therapy? Drinking outcomes with an emerging adult sample. Addict Biol. 2009;14:356-65 pubmed publisher
  15. Kang J, Kim S, Namkoong K, An S. Association of DRD4 and COMT polymorphisms with disgust sensitivity in healthy volunteers. Neuropsychobiology. 2010;61:105-12 pubmed publisher
    ..These findings suggest that disgust sensitivity may be affected by genetic components, such as dopamine-related genes. ..
  16. Larsen H, van der Zwaluw C, Overbeek G, Granic I, Franke B, Engels R. A variable-number-of-tandem-repeats polymorphism in the dopamine D4 receptor gene affects social adaptation of alcohol use: investigation of a gene-environment interaction. Psychol Sci. 2010;21:1064-8 pubmed publisher
    ..Carrying the 7-repeat allele may increase the risk for heavy alcohol use or abuse in the company of heavy-drinking peers. ..
  17. Roussos P, Giakoumaki S, Bitsios P. Cognitive and emotional processing in high novelty seeking associated with the L-DRD4 genotype. Neuropsychologia. 2009;47:1654-9 pubmed publisher
    ..The proposed role of the NS phenotype in human evolution and in disorders of impulsivity is discussed under the light of the present findings. ..
  18. Rondou P, Skieterska K, Packeu A, Lintermans B, Vanhoenacker P, Vauquelin G, et al. KLHL12-mediated ubiquitination of the dopamine D4 receptor does not target the receptor for degradation. Cell Signal. 2010;22:900-13 pubmed publisher
    ..Interestingly, KLHL12 does also interact with beta-arrestin2 but this has no effect on the ubiquitination or localization of beta-arrestin2 nor on the internalization of the D4 receptor. ..
  19. Schulze M, Siol O, Meise W, Lehmann J, Enzensperger C. Ring expansions of tetrahydroprotoberberines and related dibenzo[c,g]azecines modulate the dopamine receptor subtype affinity and selectivity. Arch Pharm (Weinheim). 2010;343:207-14 pubmed publisher
    ..Distances in energy-minimized conformations were measured in order to explain our findings. ..
  20. Eisenegger C, Knoch D, Ebstein R, Gianotti L, Sandor P, Fehr E. Dopamine receptor D4 polymorphism predicts the effect of L-DOPA on gambling behavior. Biol Psychiatry. 2010;67:702-6 pubmed publisher
  21. Spooren A, Rondou P, Debowska K, Lintermans B, Vermeulen L, Samyn B, et al. Resistance of the dopamine D4 receptor to agonist-induced internalization and degradation. Cell Signal. 2010;22:600-9 pubmed publisher
    ..Data from neuronal cell lines, which have been reported to show low endogenous D4 receptor expression, such as the hippocampal cell line HT22 and primary rat hippocampal cells, further support these observations. ..
  22. Dragan W, Oniszczenko W. The association between dopamine D4 receptor exon III polymorphism and intensity of PTSD symptoms among flood survivors. Anxiety Stress Coping. 2009;22:483-95 pubmed publisher
    ..2) of the PTSD-F than participants who did not have these alleles in genotype. The results must be treated with caution, however, due to methodological restrictions and they need to be replicated on a larger sample. ..
  23. Braszko J. Participation of D 1-4 dopamine receptors in the pro-cognitive effects of angiotensin IV and des-Phe 6 angiotensin IV. Neurosci Biobehav Rev. 2010;34:343-50 pubmed publisher
    ..The data reviewed here, demonstrating DA-Ang IV and des-Phe(6)Ang IV interactions in brain, strongly suggest probability of clinically relevant effects of concomitant use of antipsychotic and RAS affecting drugs. ..
  24. Chien C, Lin C, Chang Y, Lung F. Association of VNTR polymorphisms in the MAOA promoter and DRD4 exon 3 with heroin dependence in male Chinese addicts. World J Biol Psychiatry. 2010;11:409-16 pubmed publisher
  25. Auerbach J, Atzaba Poria N, Berger A, Landau R, Arbelle S, Raz Y, et al. Dopamine risk and paternal ADHD symptomatology associated with ADHD symptoms in four and a half-year-old boys. Psychiatr Genet. 2010;20:160-5 pubmed publisher
    ..This study adds to the growing literature on the efficacy of including multiple genetic and environmental risk factors in studies related to the development of psychopathology. ..
  26. Lauzon N, Bishop S, Laviolette S. Dopamine D1 versus D4 receptors differentially modulate the encoding of salient versus nonsalient emotional information in the medial prefrontal cortex. J Neurosci. 2009;29:4836-45 pubmed publisher
  27. Wang H, Stanwood G, Grandy D, Deutch A. Dystrophic dendrites in prefrontal cortical pyramidal cells of dopamine D1 and D2 but not D4 receptor knockout mice. Brain Res. 2009;1300:58-64 pubmed publisher
    ..The current data also suggest that caution should be exercised in the interpretation of behavioral, physiological, and biochemical studies of the prefrontal cortex in dopamine receptor knockout mice. ..
  28. Gao X, Su L, Zhao A, Luo X, Xia K. [Association of 14 polymorphisms in the five candidate genes and attention deficit hyperactivity disorder]. Zhongguo Dang Dai Er Ke Za Zhi. 2009;11:617-22 pubmed
    ..The specific combination of three sites of SNP in SNAP-25 gene and DRDI gene is found and shows an association with ADHD in 12 polymorphisms of the five candidate genes on glutamatergic/dopaminergic pathway. ..
  29. Stice E, Yokum S, Bohon C, Marti N, Smolen A. Reward circuitry responsivity to food predicts future increases in body mass: moderating effects of DRD2 and DRD4. Neuroimage. 2010;50:1618-25 pubmed publisher
  30. Kranzler H, Edenberg H. Pharmacogenetics of alcohol and alcohol dependence treatment. Curr Pharm Des. 2010;16:2141-8 pubmed
    ..We recommend that, whenever possible, treatment trials include the collection of DNA samples to permit pharmacogenetic analyses, and that such analyses look broadly for relevant genetic variation. ..
  31. Emanuele E, Boso M, Cassola F, Broglia D, Bonoldi I, Mancini L, et al. Increased dopamine DRD4 receptor mRNA expression in lymphocytes of musicians and autistic individuals: bridging the music-autism connection. Neuro Endocrinol Lett. 2010;31:122-5 pubmed
    ..Our current results provide intriguing preliminary evidence for a possible molecular link between dopamine DRD4 receptor, music and autism, possibly via mechanisms involving the reward system and the appraisal of emotions. ..
  32. Paweł K, Hauser J, Skibinska M, Szczepankiewicz A, Dmitrzak Weglarz M, Gorzkowska K, et al. [Family based association study of DRD1, DRD2, DRD3, DRD4, DAT, COMT gene polymorphism in schizophrenia]. Psychiatr Pol. 2010;44:405-13 pubmed
    ..091). This trend should be interpreted very carefully. There is also the possibility that other variant of gene in linkage disequilibrium with -48A/G polymorphism was responsible for the trend observed in this study. ..
  33. De Gendt K, McKinnell C, Willems A, Saunders P, Sharpe R, Atanassova N, et al. Organotypic cultures of prepubertal mouse testes: a method to study androgen action in sertoli cells while preserving their natural environment. Biol Reprod. 2009;81:1083-92 pubmed publisher
    ..This approach facilitates detailed analysis of their regulation in ways not possible in vivo. ..
  34. Sonuga Barke E, Oades R, Psychogiou L, Chen W, Franke B, Buitelaar J, et al. Dopamine and serotonin transporter genotypes moderate sensitivity to maternal expressed emotion: the case of conduct and emotional problems in attention deficit/hyperactivity disorder. J Child Psychol Psychiatry. 2009;50:1052-63 pubmed publisher
    ..Further research should focus on distinguishing general sensitivity genotypes from those conferring risk or protective qualities. ..
  35. Martel M, Nikolas M, Jernigan K, Friderici K, Nigg J. Personality mediation of genetic effects on Attention-Deficit/Hyperactivity Disorder. J Abnorm Child Psychol. 2010;38:633-43 pubmed publisher
    ..High neuroticism and low conscientiousness may be useful as early markers for children at risk for ADHD. ..
  36. Kubikova L, Wada K, Jarvis E. Dopamine receptors in a songbird brain. J Comp Neurol. 2010;518:741-69 pubmed publisher
    ..Our findings are consistent with hypotheses that dopamine receptors may be involved in song development and social context-dependent behaviors...
  37. Stice E, Dagher A. Genetic variation in dopaminergic reward in humans. Forum Nutr. 2010;63:176-85 pubmed publisher
    ..Improved understanding of the role of dopamine-based reward circuitry and genotypes that influence the functioning of this circuitry may inform the design of more effective preventive and treatment interventions for obesity. ..
  38. Stevenson J, Sonuga Barke E, McCann D, Grimshaw K, Parker K, Rose Zerilli M, et al. The role of histamine degradation gene polymorphisms in moderating the effects of food additives on children's ADHD symptoms. Am J Psychiatry. 2010;167:1108-15 pubmed publisher
    ..Genes influencing a range of neurotransmitter systems and their interplay with environmental factors, such as diet, need to be examined to understand genetic influences on ADHD symptoms. ..
  39. Cavallotti C, Mancone M, Bruzzone P, Sabbatini M, Mignini F. Dopamine receptor subtypes in the native human heart. Heart Vessels. 2010;25:432-7 pubmed publisher
    ..Our findings provide a favorable basis for researching the role of dopamine receptors in controlling functions of the human heart and in the pathogenesis of cardiovascular diseases. ..
  40. Levitan R, Kaplan A, Davis C, Lam R, Kennedy J. A season-of-birth/DRD4 interaction predicts maximal body mass index in women with bulimia nervosa. Neuropsychopharmacology. 2010;35:1729-33 pubmed publisher
    ..9 vs 8.8%, respectively, p=0.008). These data offer further evidence that season of birth interacts with the 7R allele of DRD4 to influence body weight regulation in female overeating populations. ..
  41. Tsuchimine S, Yasui Furukori N, Kaneda A, Saito M, Sugawara N, Kaneko S. Minor genetic variants of the dopamine D4 receptor (DRD4) polymorphism are associated with novelty seeking in healthy Japanese subjects. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:1232-5 pubmed publisher
    ..long alleles), there were no significant associations between the DRD4 VNTR polymorphism and any TCI scores. Our results suggest that minor 5-repeat allele is associated with high novelty-seeking scores in healthy Japanese subjects. ..
  42. Treister R, Pud D, Ebstein R, Laiba E, Gershon E, Haddad M, et al. Associations between polymorphisms in dopamine neurotransmitter pathway genes and pain response in healthy humans. Pain. 2009;147:187-93 pubmed publisher
    ..These results, together with the known function of the investigated candidate gene polymorphisms, suggest that low dopaminergic activity can be associated with high pain sensitivity and vice versa. ..
  43. Depoortere R, Bardin L, Rodrigues M, Abrial E, Aliaga M, Newman Tancredi A. Penile erection and yawning induced by dopamine D2-like receptor agonists in rats: influence of strain and contribution of dopamine D2, but not D3 and D4 receptors. Behav Pharmacol. 2009;20:303-11 pubmed publisher
    ..5 mg/kg). The present data do not support a major implication of either DA D3 or D4 receptors in the control of PE and YA in rats, but indicate a preponderant role of DA D2 receptors. ..
  44. Tschirren B, Bensch S. Genetics of personalities: no simple answers for complex traits. Mol Ecol. 2010;19:624-6 pubmed publisher
    ..2010) attempt to replicate this previously observed association in wild-living birds, and test for the generality of the association between DRD4 and personality across a number of European great tit populations. ..
  45. Marazziti D, Baroni S, Masala I, Giannaccini G, Betti L, Palego L, et al. [(3)H]-YM-09151-2 binding sites in human brain postmortem. Neurochem Int. 2009;55:643-7 pubmed publisher
    ..In conclusion, these findings underline that it is possible to label D(4) receptors by means of [(3)H]-YM-09151-2, provided that D(2), D(3) and sigma receptors are blocked. ..
  46. Kaitz M, Shalev I, Sapir N, Devor N, Samet Y, Mankuta D, et al. Mothers' dopamine receptor polymorphism modulates the relation between infant fussiness and sensitive parenting. Dev Psychobiol. 2010;52:149-57 pubmed publisher
    ..Among those parents, sensitivity did not vary with infant temperament. This pattern of results indicates that mothers are differentially susceptible to infant fussiness, dependent on the presence of the 7-repeat DRD4 allele. ..
  47. Becker K, Blomeyer D, El Faddagh M, Esser G, Schmidt M, Banaschewski T, et al. From regulatory problems in infancy to attention-deficit/hyperactivity disorder in childhood: a moderating role for the dopamine D4 receptor gene?. J Pediatr. 2010;156:798-803, 803.e1-803.e2 pubmed publisher
    ..The DRD4 genotype seems to moderate the association between regulatory problems in infancy and later ADHD. A replication study is needed before further conclusions can be drawn, however. ..
  48. Korsten P, Mueller J, Hermannstädter C, Bouwman K, Dingemanse N, Drent P, et al. Association between DRD4 gene polymorphism and personality variation in great tits: a test across four wild populations. Mol Ecol. 2010;19:832-43 pubmed publisher
    ..Another important future challenge is the identification of additional loci influencing avian personality traits in the wild...
  49. Collins G, Truccone A, Haji Abdi F, Newman A, Grundt P, Rice K, et al. Proerectile effects of dopamine D2-like agonists are mediated by the D3 receptor in rats and mice. J Pharmacol Exp Ther. 2009;329:210-7 pubmed publisher
    ..These studies fail to support a role for the D(4) receptor in the regulation of PE or yawning by D(2)-like agonists. ..
  50. Vaughn M, Beaver K, DeLisi M, Howard M, PERRON B. Dopamine D4 receptor gene exon III polymorphism associated with binge drinking attitudinal phenotype. Alcohol. 2009;43:179-84 pubmed publisher
    ..The present study provides unique evidence to the genetic underpinnings of binge drinking. Results suggest that the 7R allele may be an important contributor to the liability to binge drinking. ..
  51. Froehlich T, McGough J, Stein M. Progress and promise of attention-deficit hyperactivity disorder pharmacogenetics. CNS Drugs. 2010;24:99-117 pubmed publisher
  52. Campbell B, Dreber A, Apicella C, Eisenberg D, Gray P, Little A, et al. Testosterone exposure, dopaminergic reward, and sensation-seeking in young men. Physiol Behav. 2010;99:451-6 pubmed publisher
    ..These results add to earlier reports of an association between T and sensation-seeking. In addition, our results also indicate that genetic variation in DRD4 is independently associated with SSS sensation-seeking. ..
  53. Kótyuk E, Kovacs Nagy R, Faludi G, Urban R, Ronai Z, Sasvari Szekely M, et al. [Association between nicotine dependence and the -521 promoter polymorfism of the dopamine D4 receptor in patients with major depression]. Neuropsychopharmacol Hung. 2009;11:59-67 pubmed
    ..8 +/- 3.4) as compared to those without the C allele (IT: mean score = 10.l +/- 2.5), these differences were significant (p = 0.003). ..