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词条 Dopamine receptor D4
释义

  1. Genetics

      48-base pair VNTR {{anchor|DRD4-7R|DRD4–7R}} 

  2. Novelty seeking

  3. Cognition

  4. Cognitive development

  5. Ligands

     Agonists  Antagonists  Inverse agonists 

  6. See also

  7. References

  8. External links

{{Use dmy dates|date=November 2017}}{{DISPLAYTITLE:Dopamine receptor D4}}{{Infobox_gene}}

The dopamine receptor D4 is a dopamine D2-like G protein-coupled receptor encoded by the {{gene|DRD4}} gene on chromosome 11 at 11p15.5.[1]

The structure of DRD4 was recently reported in complex with the antipsychotic drug nemonapride.[2]

As with other dopamine receptor subtypes, the D4 receptor is activated by the neurotransmitter dopamine. It is linked to many neurological and psychiatric conditions[3] including schizophrenia and bipolar disorder,[4] ADHD,[5][6] addictive behaviors,[7] Parkinson's disease,[8] and eating disorders such as anorexia nervosa.[9]

It is also a target for drugs which treat schizophrenia and Parkinson's disease.[10] The D4 receptor is considered to be D2-like in which the activated receptor inhibits the enzyme adenylate cyclase, thereby reducing the intracellular concentration of the second messenger cyclic AMP.[11]

Genetics

The human protein is coded by the DRD4 on chromosome 11 located in 11p15.5.[12]

There are slight variations (mutations/polymorphisms) in the human gene:

  • A 48-base pair VNTR in exon 3
  • C-521T in the promoter
  • 13-base pair deletion of bases 235 to 247 in exon 1
  • 12 base pair repeat in exon 1[13]
  • Val194Gly
  • A polymorphic tandem duplication of 48 bp[14]

Mutations in this gene have been associated with various behavioral phenotypes, including autonomic nervous system dysfunction, attention deficit/hyperactivity disorder,[15] schizophrenia[16] and the personality trait of novelty seeking.[17]

48-base pair VNTR {{anchor|DRD4-7R|DRD4–7R}}

The 48-base pair variable number tandem repeat (VNTR) in exon 3 range from 2 to 11 repeats.[12] Dopamine is more potent at the D4 receptor with 2 allelic repeat or 7 allelic repeats than the variant with 4 allelic repeats.[18]

DRD4-7R, the 7-repeat (7R) variant of DRD4 (DRD4 7-repeat polymorphism), has been linked to a susceptibility for developing ADHD in several meta-analyses and other psychological traits and disorders.[19][20] Adults and children with the DRD4 7-repeat polymorphism show variations in auditory-evoked gamma oscillations, which may be related to attention processing.[21][22]

The frequency of the alleles varies greatly between populations, e.g., the 7-repeat version has high incidence in America and low in Asia.[23] "Long" versions of polymorphisms are the alleles with 6 to 10 repeats. 7R appears to react less strongly to dopamine molecules.[24]

The 48-base pair VNTR has been the subject of much speculation about its evolution and role in human behaviors cross-culturally. The 7R allele appears to have been selected for about 40,000 years ago.[23] In 1999 Chen and colleagues[25] observed that populations who migrated farther in the past 30,000 to 1,000 years ago had a higher frequency of 7R/long alleles. They also showed that nomadic populations had higher frequencies of 7R alleles than sedentary ones. More recently it was observed that the health status of nomadic Ariaal men was higher if they had 7R alleles. However, in recently sedentary (non-nomadic) Ariaal those with 7R alleles seemed to have slightly deteriorated health.[26]

Novelty seeking

Despite early findings of an association between the DRD4 48bp VNTR and novelty seeking (a normal characteristic of exploratory and excitable people),[27][28] a 2008 meta-analysis compared 36 published studies of novelty seeking and the polymorphism and found no effect. Results are consistent with novelty-seeking behavior being a complex trait associated with many genes, and the variance attributable to DRD4 by itself being very small. The meta-analysis of 11 studies did find that another polymorphism in the gene, the -521C/T, showed an association with novelty seeking.[17] While human results are not strong, research in animals has suggested stronger associations [29][30][31][32][33] and new evidence suggests that human encroachment may exert selection pressure in favor of DRD4 variants associated with novelty seeking.[34]{{Clarify|reason=not clear this reference has anything to do with human-related selection|date=December 2018}}

Cognition

Several studies have shown that agonists that activate the D4 receptor increase working memory performance and fear acquisition in monkeys and rodents according to a U-shaped dose response curve.[35][36][37] However, antagonists of the D4 receptor reverse stress-induced or drug-induced working memory deficits.[38][39] Gamma oscillations, which may be correlated with cognitive processing, can be increased by D4R agonists, but are not significantly reduced by D4R antagonists.[40][41][42]

Cognitive development

Several studies have suggested that parenting may affect the cognitive development of children with the 7-repeat allele of DRD4.[34] Parenting that has maternal sensitivity, mindfulness, and autonomy–support at 15 months was found to alter children's executive functions at 18 to 20 months.[34] Children with poorer quality parenting were more impulsive and sensation seeking than those with higher quality parenting.[34] Higher quality parenting was associated with better executive control in 4-year-olds.[34]

Ligands

Agonists

  • WAY-100635: potent full agonist, with 5-HT1A antagonistic component[43]
  • A-412,997: full agonist, > 100-fold selective over a panel of seventy different receptors and ion channels[44]
  • ABT-724 - developed for treatment of erectile dysfunction[45]
  • ABT-670 - better oral bioavailability than ABT-724[46]
  • FAUC 316: partial agonist, > 8600-fold selective over other dopamine receptor subtypes[47]
  • FAUC 299: partial agonist[47]
  • (E)-1-aryl-3-(4-pyridinepiperazin-1-yl)propanone oximes[48]
  • PIP3EA: partial agonist[49]
  • Flibanserin - partial agonist
  • PD-168,077 - D4 selective but also binds to α1A, α2C and 5HT1A
  • CP-226,269 - D4 selective but also binds to D2, D3, α2A, α2C and 5HT1A
  • Ro10-5824 – partial agonist
  • Roxindole – D4 selective but also D2 and D3 autoreceptor agonist, 5HT1A receptor agonist, serotonin reuptake inhibitor)
  • Apomorphine – D4 selective but also D2 and D3 agonist, α-adrenergic and serotonergic weak antagonist

Antagonists

  • A-381393: potent, subtype selective antagonist (>2700-fold)[50]
  • FAUC 213[59]
  • L-745,870[51][52]
  • L-750,667[53]
  • ML-398[54]
  • S 18126 - also σ1 affinity[55]
  • Fananserin – mixed 5-HT2A / D4 antagonist
  • Olanzapine, an atypical antipsychotic
  • Buspirone, an anxiolytic

Inverse agonists

  • FAUC F41: inverse agonist, subtype selectivity of more than 3 orders of magnitude over D2 and D3[56][57]

See also

  • dopamine hypothesis of psychosis

References

1. ^{{cite journal | vauthors = Van Tol HH, Bunzow JR, Guan HC, Sunahara RK, Seeman P, Niznik HB, Civelli O | title = Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine | journal = Nature | volume = 350 | issue = 6319 | pages = 610–4 | date = April 1991 | pmid = 1840645 | doi = 10.1038/350610a0 }}
2. ^{{cite journal | vauthors = Wang S, Wacker D, Levit A, Che T, Betz RM, McCorvy JD, Venkatakrishnan AJ, Huang XP, Dror RO, Shoichet BK, Roth BL | title = D4 dopamine receptor high-resolution structures enable the discovery of selective agonists | journal = Science | volume = 358 | issue = 6361 | pages = 381–386 | date = October 2017 | pmid = 29051383 | pmc = 5856174 | doi = 10.1126/science.aan5468 }}
3. ^{{cite journal | vauthors = Ptácek R, Kuzelová H, Stefano GB | title = Dopamine D4 receptor gene DRD4 and its association with psychiatric disorders | journal = Medical Science Monitor | volume = 17 | issue = 9 | pages = RA215–20 | date = September 2011 | pmid = 21873960 | pmc = 3560519 | doi = 10.12659/MSM.881925 }}
4. ^{{cite journal | vauthors = Domschke K | title = Clinical and molecular genetics of psychotic depression | journal = Schizophrenia Bulletin | volume = 39 | issue = 4 | pages = 766–75 | date = July 2013 | pmid = 23512949 | pmc = 3686457 | doi = 10.1093/schbul/sbt040 }}
5. ^{{cite journal | vauthors = LaHoste GJ, Swanson JM, Wigal SB, Glabe C, Wigal T, King N, Kennedy JL | title = Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder | journal = Molecular Psychiatry | volume = 1 | issue = 2 | pages = 121–4 | date = May 1996 | pmid = 9118321 }}
6. ^{{cite journal | vauthors = Smalley SL, Bailey JN, Palmer CG, Cantwell DP, McGough JJ, Del'Homme MA, Asarnow JR, Woodward JA, Ramsey C, Nelson SF | title = Evidence that the dopamine D4 receptor is a susceptibility gene in attention deficit hyperactivity disorder | journal = Molecular Psychiatry | volume = 3 | issue = 5 | pages = 427–30 | date = September 1998 | pmid = 9774776 | doi = 10.1038/sj.mp.4000457 }}
7. ^{{cite journal | vauthors = McGeary J | title = The DRD4 exon 3 VNTR polymorphism and addiction-related phenotypes: a review | journal = Pharmacology Biochemistry and Behavior | volume = 93 | issue = 3 | pages = 222–9 | date = September 2009 | pmid = 19336242 | pmc = 2706302 | doi = 10.1016/j.pbb.2009.03.010 }}
8. ^{{cite journal | vauthors = Cormier F, Muellner J, Corvol JC | title = Genetics of impulse control disorders in Parkinson's disease | journal = Journal of Neural Transmission | volume = 120 | issue = 4 | pages = 665–71 | date = April 2013 | pmid = 23232665 | doi = 10.1007/s00702-012-0934-4 }}
9. ^{{cite journal | vauthors = Rask-Andersen M, Olszewski PK, Levine AS, Schiöth HB | title = Molecular mechanisms underlying anorexia nervosa: focus on human gene association studies and systems controlling food intake | journal = Brain Research Reviews | volume = 62 | issue = 2 | pages = 147–64 | date = March 2010 | pmid = 19931559 | doi = 10.1016/j.brainresrev.2009.10.007 }}
10. ^{{cite journal | vauthors = Ptáček R, Kuželová H, Stefano GB, Raboch J, Kream RM | title = Targeted D4 dopamine receptors: implications for drug discovery and therapeutic development | journal = Current Drug Targets | volume = 14 | issue = 4 | pages = 507–12 | date = April 2013 | pmid = 23469923 | doi = 10.2174/1389450111314040012 }}
11. ^{{cite journal | vauthors = Neve KA, Seamans JK, Trantham-Davidson H | title = Dopamine receptor signaling | journal = Journal of Receptor and Signal Transduction Research | volume = 24 | issue = 3 | pages = 165–205 | date = August 2004 | pmid = 15521361 | doi = 10.1081/RRS-200029981 | citeseerx = 10.1.1.465.5011 }}
12. ^1 {{cite journal | vauthors = Van Tol HH, Wu CM, Guan HC, Ohara K, Bunzow JR, Civelli O, Kennedy J, Seeman P, Niznik HB, Jovanovic V | title = Multiple dopamine D4 receptor variants in the human population | journal = Nature | volume = 358 | issue = 6382 | pages = 149–52 | date = July 1992 | pmid = 1319557 | doi = 10.1038/358149a0 }}
13. ^{{cite journal | vauthors = Catalano M, Nobile M, Novelli E, Nöthen MM, Smeraldi E | title = Distribution of a novel mutation in the first exon of the human dopamine D4 receptor gene in psychotic patients | journal = Biological Psychiatry | volume = 34 | issue = 7 | pages = 459–64 | date = October 1993 | pmid = 8268330 | doi = 10.1016/0006-3223(93)90236-7 }}
14. ^{{cite journal | vauthors = Rondou P, Haegeman G, Van Craenenbroeck K | title = The dopamine D4 receptor: biochemical and signalling properties | journal = Cellular and Molecular Life Sciences | volume = 67 | issue = 12 | pages = 1971–86 | date = June 2010 | pmid = 20165900 | doi = 10.1007/s00018-010-0293-y }}
15. ^{{cite journal | vauthors = Thapar A, Langley K, Owen MJ, O'Donovan MC | title = Advances in genetic findings on attention deficit hyperactivity disorder | journal = Psychological Medicine | volume = 37 | issue = 12 | pages = 1681–92 | date = December 2007 | pmid = 17506925 | doi = 10.1017/S0033291707000773 }}
16. ^Gene Overview of All Published Schizophrenia-Association Studies for DRD4 {{webarchive|url=https://web.archive.org/web/20090221130224/http://schizophreniaforum.org/res/sczgene/geneoverview.asp?geneid=94 |date=21 February 2009 }} – SzGene database at Schizophrenia Research Forum.
17. ^1 {{cite journal | vauthors = Munafò MR, Yalcin B, Willis-Owen SA, Flint J | title = Association of the dopamine D4 receptor (DRD4) gene and approach-related personality traits: meta-analysis and new data | journal = Biological Psychiatry | volume = 63 | issue = 2 | pages = 197–206 | date = January 2008 | pmid = 17574217 | doi = 10.1016/j.biopsych.2007.04.006 }}
18. ^{{cite journal | vauthors = Wedemeyer C, Goutman JD, Avale ME, Franchini LF, Rubinstein M, Calvo DJ | title = Functional activation by central monoamines of human dopamine D(4) receptor polymorphic variants coupled to GIRK channels in Xenopus oocytes | journal = European Journal of Pharmacology | volume = 562 | issue = 3 | pages = 165–73 | date = May 2007 | pmid = 17350612 | doi = 10.1016/j.ejphar.2007.01.055 }}
19. ^{{cite journal | vauthors = Wu J, Xiao H, Sun H, Zou L, Zhu LQ | title = Role of dopamine receptors in ADHD: a systematic meta-analysis | journal = Molecular Neurobiology | volume = 45 | issue = 3 | pages = 605–20 | date = June 2012 | pmid = 22610946 | doi = 10.1007/s12035-012-8278-5 }}
20. ^{{cite journal | vauthors = Faraone SV, Doyle AE, Mick E, Biederman J | title = Meta-analysis of the association between the 7-repeat allele of the dopamine D(4) receptor gene and attention deficit hyperactivity disorder | journal = The American Journal of Psychiatry | volume = 158 | issue = 7 | pages = 1052–7 | date = July 2001 | pmid = 11431226 | doi = 10.1176/appi.ajp.158.7.1052 }}
21. ^{{cite journal | vauthors = Yordanova J, Banaschewski T, Kolev V, Woerner W, Rothenberger A | title = Abnormal early stages of task stimulus processing in children with attention-deficit hyperactivity disorder--evidence from event-related gamma oscillations | journal = Clinical Neurophysiology | volume = 112 | issue = 6 | pages = 1096–108 | date = June 2001 | pmid = 11377270 | doi=10.1016/s1388-2457(01)00524-7}}
22. ^{{cite journal | vauthors = Demiralp T, Herrmann CS, Erdal ME, Ergenoglu T, Keskin YH, Ergen M, Beydagi H | title = DRD4 and DAT1 polymorphisms modulate human gamma band responses | journal = Cerebral Cortex | volume = 17 | issue = 5 | pages = 1007–19 | date = May 2007 | pmid = 16751296 | doi = 10.1093/cercor/bhl011 }}
23. ^1 {{cite journal | vauthors = Wang E, Ding YC, Flodman P, Kidd JR, Kidd KK, Grady DL, Ryder OA, Spence MA, Swanson JM, Moyzis RK | title = The genetic architecture of selection at the human dopamine receptor D4 (DRD4) gene locus | journal = American Journal of Human Genetics | volume = 74 | issue = 5 | pages = 931–44 | date = May 2004 | pmid = 15077199 | pmc = 1181986 | doi = 10.1086/420854 }}
24. ^{{cite journal | vauthors = Asghari V, Sanyal S, Buchwaldt S, Paterson A, Jovanovic V, Van Tol HH | title = Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants | journal = Journal of Neurochemistry | volume = 65 | issue = 3 | pages = 1157–65 | date = September 1995 | pmid = 7643093 | doi = 10.1046/j.1471-4159.1995.65031157.x }}
25. ^{{cite journal |vauthors=Chen CS, Burton M, Greenberger E, Dmitrieva J |title=Population Migration and the Variation of Dopamine D4 Receptor (DRD4) Allele Frequencies Around the Globe |journal=Evolution and Human Behavior |volume=20 |issue=5 |year=1999 |pages=309–24 |doi=10.1016/S1090-5138(99)00015-X |url=http://www.escholarship.org/uc/item/7br14384 }}
26. ^{{cite journal | vauthors = Eisenberg DT, Campbell B, Gray PB, Sorenson MD | title = Dopamine receptor genetic polymorphisms and body composition in undernourished pastoralists: an exploration of nutrition indices among nomadic and recently settled Ariaal men of northern Kenya | journal = BMC Evolutionary Biology | volume = 8 | issue = | pages = 173 | date = June 2008 | pmid = 18544160 | pmc = 2440754 | doi = 10.1186/1471-2148-8-173 }}
27. ^{{cite journal | vauthors = Ebstein RP, Novick O, Umansky R, Priel B, Osher Y, Blaine D, Bennett ER, Nemanov L, Katz M, Belmaker RH | title = Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking | journal = Nature Genetics | volume = 12 | issue = 1 | pages = 78–80 | date = January 1996 | pmid = 8528256 | doi = 10.1038/ng0196-78 }}
28. ^{{cite journal | vauthors = Benjamin J, Li L, Patterson C, Greenberg BD, Murphy DL, Hamer DH | title = Population and familial association between the D4 dopamine receptor gene and measures of Novelty Seeking | journal = Nature Genetics | volume = 12 | issue = 1 | pages = 81–4 | date = January 1996 | pmid = 8528258 | doi = 10.1038/ng0196-81 }}
29. ^{{cite journal | vauthors = Fidler AE, van Oers K, Drent PJ, Kuhn S, Mueller JC, Kempenaers B | title = Drd4 gene polymorphisms are associated with personality variation in a passerine bird | journal = Proceedings: Biological Sciences | volume = 274 | issue = 1619 | pages = 1685–91 | date = July 2007 | pmid = 17472912 | pmc = 1914334 | doi = 10.1098/rspb.2007.0337 }}
30. ^{{cite journal | vauthors = Mueller JC, Edelaar P, Carrete M, Serrano D, Potti J, Blas J, Dingemanse NJ, Kempenaers B, Tella JL | title = Behaviour-related DRD4 polymorphisms in invasive bird populations | journal = Molecular Ecology | volume = 23 | issue = 11 | pages = 2876–85 | date = June 2014 | pmid = 24750181 | doi = 10.1111/mec.12763 | hdl = 10261/101638 }}
31. ^{{cite journal | vauthors = Ninomiya S, Anjiki A, Nishide Y, Mori M, Deguchi Y, Satoh T | title = Polymorphisms of the Dopamine D4 Receptor Gene in Stabled Horses are Related to Differences in Behavioral Response to Frustration | journal = Animals | volume = 3 | issue = 3 | pages = 663–9 | date = July 2013 | pmid = 26479526 | pmc = 4494454 | doi = 10.3390/ani3030663 }}
32. ^{{cite journal | vauthors = Hori Y, Ozaki T, Yamada Y, Tozaki T, Kim HS, Takimoto A, Endo M, Manabe N, Inoue-Murayama M, Fujita K | title = Breed Differences in Dopamine Receptor D4 Gene (DRD4) in Horses | journal = Journal of Equine Science | volume = 24 | issue = 3 | pages = 31–6 | year = 2013 | pmid = 24833999 | pmc = 4013985 | doi = 10.1294/jes.24.31 }}
33. ^{{cite journal | vauthors = Hejjas K, Vas J, Topal J, Szantai E, Ronai Z, Szekely A, Kubinyi E, Horvath Z, Sasvari-Szekely M, Miklosi A | title = Association of polymorphisms in the dopamine D4 receptor gene and the activity-impulsivity endophenotype in dogs | journal = Animal Genetics | volume = 38 | issue = 6 | pages = 629–33 | date = December 2007 | pmid = 17986156 | doi = 10.1111/j.1365-2052.2007.01657.x }}
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35. ^{{cite journal | vauthors = Bernaerts P, Tirelli E | title = Facilitatory effect of the dopamine D4 receptor agonist PD168,077 on memory consolidation of an inhibitory avoidance learned response in C57BL/6J mice | journal = Behavioural Brain Research | volume = 142 | issue = 1–2 | pages = 41–52 | date = June 2003 | pmid = 12798264 | doi = 10.1016/s0166-4328(02)00371-6 }}
36. ^{{cite journal | vauthors = Browman KE, Curzon P, Pan JB, Molesky AL, Komater VA, Decker MW, Brioni JD, Moreland RB, Fox GB | title = A-412997, a selective dopamine D4 agonist, improves cognitive performance in rats | journal = Pharmacology Biochemistry and Behavior | volume = 82 | issue = 1 | pages = 148–55 | date = September 2005 | pmid = 16154186 | doi = 10.1016/j.pbb.2005.08.002 }}
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38. ^{{cite journal | vauthors = Jentsch JD, Taylor JR, Redmond DE, Elsworth JD, Youngren KD, Roth RH | title = Dopamine D4 receptor antagonist reversal of subchronic phencyclidine-induced object retrieval/detour deficits in monkeys | journal = Psychopharmacology | volume = 142 | issue = 1 | pages = 78–84 | date = February 1999 | pmid = 10102786 | doi = 10.1007/s002130050865 }}
39. ^{{cite journal | vauthors = Arnsten AF, Murphy B, Merchant K | title = The selective dopamine D4 receptor antagonist, PNU-101387G, prevents stress-induced cognitive deficits in monkeys | journal = Neuropsychopharmacology | volume = 23 | issue = 4 | pages = 405–10 | date = October 2000 | pmid = 10989267 | doi = 10.1016/S0893-133X(00)00133-0 }}
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42. ^{{cite journal | vauthors = Nakazawa S, Murai T, Miyauchi M, Kotani M, Ikeda K | title = Behavioral and neurophysiological effects of Ro 10-5824, a dopamine D4 receptor partial agonist, in common marmosets | journal = Psychopharmacology | volume = 232 | issue = 17 | pages = 3287–95 | date = September 2015 | pmid = 26041337 | doi = 10.1007/s00213-015-3978-y }}
43. ^{{cite journal | vauthors = Chemel BR, Roth BL, Armbruster B, Watts VJ, Nichols DE | title = WAY-100635 is a potent dopamine D4 receptor agonist | journal = Psychopharmacology | volume = 188 | issue = 2 | pages = 244–51 | date = October 2006 | pmid = 16915381 | doi = 10.1007/s00213-006-0490-4 }}
44. ^{{cite journal | vauthors = Moreland RB, Patel M, Hsieh GC, Wetter JM, Marsh K, Brioni JD | title = A-412997 is a selective dopamine D4 receptor agonist in rats | journal = Pharmacology Biochemistry and Behavior | volume = 82 | issue = 1 | pages = 140–7 | date = September 2005 | pmid = 16153699 | doi = 10.1016/j.pbb.2005.08.001 }}
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External links

  • {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2258 | title = Dopamine Receptors: D4 | accessdate = | author = | authorlink = | date = | format = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | quote = }}
  • [https://web.archive.org/web/20110710193406/http://search.engrant.com/sp/DRD4/ Current Research on the DRD4 Gene]
  • {{MeshName|Receptors,+Dopamine+D4}}
  • {{cite web | url = http://www.bio.davidson.edu/courses/genomics/2001/wilson/gene.html | title = Are you a thrill seeker?? | accessdate = 5 April 2008 | author = Marisa Wilson | authorlink = | date = | website = | publisher = Davidson College | pages = | quote = }}
  • {{cite web | url = http://www.d4dr.net/d4dr_gene.htm | title = The D4DR Gene| accessdate = 5 April 2008 | author = | authorlink = | date = | website = | publisher = D4DR Club | pages = | archiveurl =https://web.archive.org/web/20071013035446/http://www.d4dr.net/d4dr_gene.htm| archivedate =13 October 2007| dead-url = yes | quote = }}
{{NLM content}}{{G protein-coupled receptors}}{{DEFAULTSORT:Dopamine Receptor D4}}

3 : Dopamine receptors|Biology of attention deficit hyperactivity disorder|Genes on human chromosome 11
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