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Evidence against dopamine D1/D2 receptor heteromers

Molecular Psychiatry volume 20, pages 1373–1385 (2015)Cite this article

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Abstract

Hetero-oligomers of G-protein-coupled receptors have become the subject of intense investigation, because their purported potential to manifest signaling and pharmacological properties that differ from the component receptors makes them highly attractive for the development of more selective pharmacological treatments. In particular, dopamine D1 and D2 receptors have been proposed to form hetero-oligomers that couple to Gαq proteins, and SKF83959 has been proposed to act as a biased agonist that selectively engages these receptor complexes to activate Gαq and thus phospholipase C. D1/D2 heteromers have been proposed as relevant to the pathophysiology and treatment of depression and schizophrenia. We used in vitro bioluminescence resonance energy transfer, ex vivo analyses of receptor localization and proximity in brain slices, and behavioral assays in mice to characterize signaling from these putative dimers/oligomers. We were unable to detect Gαq or Gα11 protein coupling to homomers or heteromers of D1 or D2 receptors using a variety of biosensors. SKF83959-induced locomotor and grooming behaviors were eliminated in D1 receptor knockout (KO) mice, verifying a key role for D1-like receptor activation. In contrast, SKF83959-induced motor responses were intact in D2 receptor and Gαq KO mice, as well as in knock-in mice expressing a mutant Ala286-CaMKIIα that cannot autophosphorylate to become active. Moreover, we found that, in the shell of the nucleus accumbens, even in neurons in which D1 and D2 receptor promoters are both active, the receptor proteins are segregated and do not form complexes. These data are not compatible with SKF83959 signaling through Gαq or through a D1/D2 heteromer and challenge the existence of such a signaling complex in the adult animals that we used for our studies.

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References

  1. Ferre S, Baler R, Bouvier M, Caron MG, Devi LA, Durroux T et al. Building a new conceptual framework for receptor heteromers. Nat Chem Biol 2009; 5: 131–134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Gurevich VV, Gurevich EV . GPCR monomers and oligomers: it takes all kinds. Trends Neurosci 2008; 31: 74–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lambert NA, Javitch JA . CrossTalk opposing view: weighing the evidence for class A GPCR dimers, the jury is still out. J Physiol 2014; 592 (Pt 12): 2443–2445.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Han Y, Moreira IS, Urizar E, Weinstein H, Javitch JA . Allosteric communication between protomers of dopamine class A GPCR dimers modulates activation. Nat Chem Biol 2009; 5: 688–695.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Urizar E, Yano H, Kolster R, Gales C, Lambert N, Javitch JA . CODA-RET reveals functional selectivity as a result of GPCR heteromerization. Nat Chem Biol 2011; 7: 624–630.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bertran-Gonzalez J, Herve D, Girault JA, Valjent E . What is the degree of segregation between striatonigral and striatopallidal projections? Front Neuroanatomy 2010; 4: 136.

    Article  Google Scholar 

  7. Le Moine C, Bloch B . D1 and D2 dopamine receptor gene expression in the rat striatum: sensitive cRNA probes demonstrate prominent segregation of D1 and D2 mRNAs in distinct neuronal populations of the dorsal and ventral striatum. J Comp Neurol 1995; 355: 418–426.

    Article  CAS  PubMed  Google Scholar 

  8. Perreault ML, Fan T, Alijaniaram M, O'Dowd BF, George SR . Dopamine D1-D2 receptor heteromer in dual phenotype GABA/glutamate-coexpressing striatal medium spiny neurons: regulation of BDNF, GAD67 and VGLUT1/2. PloS One 2012; 7: e33348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Perreault ML, Hasbi A, Alijaniaram M, Fan T, Varghese G, Fletcher PJ et al. The dopamine D1-D2 receptor heteromer localizes in dynorphin/enkephalin neurons: increased high affinity state following amphetamine and in schizophrenia. J Biol Chem 2010; 285: 36625–36634.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Perreault ML, Hasbi A, O'Dowd BF, George SR . The dopamine D1-D2 receptor heteromer in striatal medium spiny neurons: evidence for a third distinct neuronal pathway in basal ganglia. Front Neuroanatomy 2011; 5: 31.

    Article  Google Scholar 

  11. Deng YP, Lei WL, Reiner A . Differential perikaryal localization in rats of D1 and D2 dopamine receptors on striatal projection neuron types identified by retrograde labeling. J Chem Neuroanatomy 2006; 32: 101–116.

    Article  CAS  Google Scholar 

  12. Aizman O, Brismar H, Uhlen P, Zettergren E, Levey AI, Forssberg H et al. Anatomical and physiological evidence for D1 and D2 dopamine receptor colocalization in neostriatal neurons. Nat Neurosci 2000; 3: 226–230.

    Article  CAS  PubMed  Google Scholar 

  13. Bertran-Gonzalez J, Bosch C, Maroteaux M, Matamales M, Herve D, Valjent E et al. Opposing patterns of signaling activation in dopamine D1 and D2 receptor-expressing striatal neurons in response to cocaine and haloperidol. J Neurosci 2008; 28: 5671–5685.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Beaulieu JM, Gainetdinov RR . The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev 2011; 63: 182–217.

    Article  CAS  PubMed  Google Scholar 

  15. Undie AS, Friedman E . Stimulation of a dopamine D1 receptor enhances inositol phosphates formation in rat brain. J Pharmacol Exp Ther 1990; 253: 987–992.

    CAS  PubMed  Google Scholar 

  16. Undie AS, Weinstock J, Sarau HM, Friedman E . Evidence for a distinct D1-like dopamine receptor that couples to activation of phosphoinositide metabolism in brain. J Neurochem 1994; 62: 2045–2048.

    Article  CAS  PubMed  Google Scholar 

  17. Undie AS, Berki AC, Beardsley K . Dopaminergic behaviors and signal transduction mediated through adenylate cyclase and phospholipase C pathways. Neuropharmacology 2000; 39: 75–87.

    Article  CAS  PubMed  Google Scholar 

  18. Mahan LC, Burch RM, Monsma FJ Jr., Sibley DR . Expression of striatal D1 dopamine receptors coupled to inositol phosphate production and Ca2+ mobilization in Xenopus oocytes. Proc Natl Acad Sci USA 1990; 87: 2196–2200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Arnt J, Hyttel J, Sanchez C . Partial and full dopamine D1 receptor agonists in mice and rats: relation between behavioural effects and stimulation of adenylate cyclase activity in vitro. Eur J Pharmacol 1992; 213: 259–267.

    Article  CAS  PubMed  Google Scholar 

  20. Jin LQ, Goswami S, Cai G, Zhen X, Friedman E . SKF83959 selectively regulates phosphatidylinositol-linked D1 dopamine receptors in rat brain. J Neurochem 2003; 85: 378–386.

    Article  CAS  PubMed  Google Scholar 

  21. Panchalingam S, Undie AS . SKF83959 exhibits biochemical agonism by stimulating [(35)S]GTP gamma S binding and phosphoinositide hydrolysis in rat and monkey brain. Neuropharmacology 2001; 40: 826–837.

    Article  CAS  PubMed  Google Scholar 

  22. Andringa G, Drukarch B, Leysen JE, Cools AR, Stoof JC . The alleged dopamine D1 receptor agonist SKF 83959 is a dopamine D1 receptor antagonist in primate cells and interacts with other receptors. Eur J Pharmacol 1999; 364: 33–41.

    Article  CAS  PubMed  Google Scholar 

  23. Lee SM, Kant A, Blake D, Murthy V, Boyd K, Wyrick SJ et al. SKF-83959 is not a highly-biased functionally selective D dopamine receptor ligand with activity at phospholipase C. Neuropharmacology 2014; 86: 145–154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ryman-Rasmussen JP, Nichols DE, Mailman RB . Differential activation of adenylate cyclase and receptor internalization by novel dopamine D1 receptor agonists. Mol Pharmacol 2005; 68: 1039–1048.

    Article  CAS  PubMed  Google Scholar 

  25. Rashid AJ, So CH, Kong MM, Furtak T, El-Ghundi M, Cheng R et al. D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum. Proc Natl Acad Sci USA 2007; 104: 654–659.

    Article  CAS  PubMed  Google Scholar 

  26. Ng J, Rashid AJ, So CH, O'Dowd BF, George SR . Activation of calcium/calmodulin-dependent protein kinase IIalpha in the striatum by the heteromeric D1-D2 dopamine receptor complex. Neuroscience 2010; 165: 535–541.

    Article  CAS  PubMed  Google Scholar 

  27. Pei L, Li S, Wang M, Diwan M, Anisman H, Fletcher PJ et al. Uncoupling the dopamine D1-D2 receptor complex exerts antidepressant-like effects. Nat Med 2010; 16: 1393–1395.

    Article  CAS  PubMed  Google Scholar 

  28. Hasbi A, Fan T, Alijaniaram M, Nguyen T, Perreault ML, O'Dowd BF et al. Calcium signaling cascade links dopamine D1-D2 receptor heteromer to striatal BDNF production and neuronal growth. Proc Natl Acad Sci USA 2009; 106: 21377–21382.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zhang X, Zhou Z, Wang D, Li A, Yin Y, Gu X et al. Activation of phosphatidylinositol-linked D1-like receptor modulates FGF-2 expression in astrocytes via IP3-dependent Ca2+ signaling. J Neurosci 2009; 29: 7766–7775.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ma LQ, Liu C, Wang F, Xie N, Gu J, Fu H et al. Activation of phosphatidylinositol-linked novel D1 dopamine receptors inhibits high-voltage-activated Ca2+ currents in primary cultured striatal neurons. J Neurophysiol 2009; 101: 2230–2238.

    Article  CAS  PubMed  Google Scholar 

  31. Liu J, Wang W, Wang F, Cai F, Hu ZL, Yang YJ et al. Phosphatidylinositol-linked novel D(1) dopamine receptor facilitates long-term depression in rat hippocampal CA1 synapses. Neuropharmacology 2009; 57: 164–171.

    Article  CAS  PubMed  Google Scholar 

  32. Chu HY, Yang Z, Zhao B, Jin GZ, Hu GY, Zhen X . Activation of phosphatidylinositol-linked D1-like receptors increases spontaneous glutamate release in rat somatosensory cortical neurons in vitro. Brain Res 2010; 1343: 20–27.

    Article  CAS  PubMed  Google Scholar 

  33. Friedman E, Jin LQ, Cai GP, Hollon TR, Drago J, Sibley DR et al. D1-like dopaminergic activation of phosphoinositide hydrolysis is independent of D1A dopamine receptors: evidence from D1A knockout mice. Mol Pharmacol 1997; 51: 6–11.

    Article  CAS  PubMed  Google Scholar 

  34. Sahu A, Tyeryar KR, Vongtau HO, Sibley DR, Undieh AS . D5 dopamine receptors are required for dopaminergic activation of phospholipase C. Mol Pharmacol 2009; 75: 447–453.

    Article  CAS  PubMed  Google Scholar 

  35. Chun LS, Free RB, Doyle TB, Huang XP, Rankin ML, Sibley DR . D1-D2 dopamine receptor synergy Promotes calcium signaling via multiple mechanisms. Mol Pharmacol 2013; 84: 190–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Guo W, Shi L, Javitch JA . The fourth transmembrane segment forms the interface of the dopamine D2 receptor homodimer. J Biol Chem 2003; 278: 4385–4388.

    Article  CAS  PubMed  Google Scholar 

  37. Guo W, Urizar E, Kralikova M, Mobarec JC, Shi L, Filizola M et al. Dopamine D2 receptors form higher order oligomers at physiological expression levels. EMBO J 2008; 27: 2293–2304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Gales C, Rebois RV, Hogue M, Trieu P, Breit A, Hebert TE et al. Real-time monitoring of receptor and G-protein interactions in living cells. Nat Methods 2005; 2: 177–184.

    Article  CAS  PubMed  Google Scholar 

  39. Drago J, Gerfen CR, Lachowicz JE, Steiner H, Hollon TR, Love PE et al. Altered striatal function in a mutant mouse lacking D1A dopamine receptors. Proc Natl Acad Sci USA 1994; 91: 12564–12568.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Jung MY, Skryabin BV, Arai M, Abbondanzo S, Fu D, Brosius J et al. Potentiation of the D2 mutant motor phenotype in mice lacking dopamine D2 and D3 receptors. Neuroscience 1999; 91: 911–924.

    Article  CAS  PubMed  Google Scholar 

  41. Hollon TR, Bek MJ, Lachowicz JE, Ariano MA, Mezey E, Ramachandran R et al. Mice lacking D5 dopamine receptors have increased sympathetic tone and are hypertensive. J Neurosci 2002; 22: 10801–10810.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Frederick AL, Saborido TP, Stanwood GD . Neurobehavioral phenotyping of G(alphaq) knockout mice reveals impairments in motor functions and spatial working memory without changes in anxiety or behavioral despair. Front Behav Neurosci 2012; 6: 29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Shuen JA, Chen M, Gloss B, Calakos N . Drd1a-tdTomato BAC transgenic mice for simultaneous visualization of medium spiny neurons in the direct and indirect pathways of the basal ganglia. J Neurosci 2008; 28: 2681–2685.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Gong S, Zheng C, Doughty ML, Losos K, Didkovsky N, Schambra UB et al. A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature 2003; 425: 917–925.

    Article  CAS  PubMed  Google Scholar 

  45. Ade KK, Wan Y, Chen M, Gloss B, Calakos N . An Improved BAC transgenic fluorescent reporter line for sensitive and specific identification of striatonigral medium spiny neurons. Front Systems Neurosci 2011; 5: 32.

    Article  CAS  Google Scholar 

  46. Trifilieff P, Feng B, Urizar E, Winiger V, Ward RD, Taylor KM et al. Increasing dopamine D2 receptor expression in the adult nucleus accumbens enhances motivation. Mol Psychiatry 2013; 18: 1025–1033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Trifilieff P, Rives ML, Urizar E, Piskorowski RA, Vishwasrao HD, Castrillon J et al. Detection of antigen interactions ex vivo by proximity ligation assay: endogenous dopamine D2-adenosine A2A receptor complexes in the striatum. BioTechniques 2011; 51: 111–118.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Sonntag KC, Brenhouse HC, Freund N, Thompson BS, Puhl M, Andersen SL . Viral over-expression of D1 dopamine receptors in the prefrontal cortex increase high-risk behaviors in adults: comparison with adolescents. Psychopharmacology 2014; 231: 1615–1626.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Gales C, Van Durm JJ, Schaak S, Pontier S, Percherancier Y, Audet M et al. Probing the activation-promoted structural rearrangements in preassembled receptor-G protein complexes. Nat Struct Mol Biol 2006; 13: 778–786.

    Article  CAS  PubMed  Google Scholar 

  50. Sauliere A, Bellot M, Paris H, Denis C, Finana F, Hansen JT et al. Deciphering biased-agonism complexity reveals a new active AT1 receptor entity. Nat Chem Biol 2012; 8: 622–630.

    Article  CAS  PubMed  Google Scholar 

  51. So CH, Verma V, Alijaniaram M, Cheng R, Rashid AJ, O'Dowd BF et al. Calcium signaling by dopamine D5 receptor and D5-D2 receptor hetero-oligomers occurs by a mechanism distinct from that for dopamine D1-D2 receptor hetero-oligomers. Mol Pharmacol 2009; 75: 843–854.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Hasbi A, O'Dowd BF, George SR . Heteromerization of dopamine D2 receptors with dopamine D1 or D5 receptors generates intracellular calcium signaling by different mechanisms. Curr Opin Pharmacol 2010; 10: 93–99.

    Article  CAS  PubMed  Google Scholar 

  53. Downes RP, Waddington JL . Grooming and vacuous chewing induced by SK&F 83959, an agonist of dopamine 'D1-like' receptors that inhibits dopamine-sensitive adenylyl cyclase. Eur J Pharmacol 1993; 234: 135–136.

    Article  CAS  PubMed  Google Scholar 

  54. Deveney AM, Waddington JL . Pharmacological characterization of behavioural responses to SK&F 83959 in relation to 'D1-like' dopamine receptors not linked to adenylyl cyclase. Br J Pharmacol 1995; 116: 2120–2126.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Zhen X, Goswami S, Abdali SA, Gil M, Bakshi K, Friedman E . Regulation of cyclin-dependent kinase 5 and calcium/calmodulin-dependent protein kinase II by phosphatidylinositol-linked dopamine receptor in rat brain. Mol Pharmacol 2004; 66: 1500–1507.

    Article  CAS  PubMed  Google Scholar 

  56. Gustin RM, Shonesy BC, Robinson SL, Rentz TJ, Baucum AJ 2nd, Jalan-Sakrikar N et al. Loss of Thr286 phosphorylation disrupts synaptic CaMKIIalpha targeting, NMDAR activity and behavior in pre-adolescent mice. Mol Cell Neurosci 2011; 47: 286–292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Giese KP, Fedorov NB, Filipkowski RK, Silva AJ . Autophosphorylation at Thr286 of the alpha calcium-calmodulin kinase II in LTP and learning. Science 1998; 279: 870–873.

    Article  CAS  PubMed  Google Scholar 

  58. Gerfen CR . The neostriatal mosaic: multiple levels of compartmental organization. Trends Neurosci 1992; 15: 133–139.

    Article  CAS  PubMed  Google Scholar 

  59. Hersch SM, Ciliax BJ, Gutekunst CA, Rees HD, Heilman CJ, Yung KK et al. Electron microscopic analysis of D1 and D2 dopamine receptor proteins in the dorsal striatum and their synaptic relationships with motor corticostriatal afferents. J Neurosci 1995; 15 (Pt 2): 5222–5237.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Gangarossa G, Espallergues J, de Kerchove d'Exaerde A, El Mestikawy S, Gerfen CR, Herve D et al. Distribution and compartmental organization of GABAergic medium-sized spiny neurons in the mouse nucleus accumbens. Front Neural Circuits 2013; 7: 22.

    PubMed  PubMed Central  Google Scholar 

  61. Yung KK, Bolam JP, Smith AD, Hersch SM, Ciliax BJ, Levey AI . Immunocytochemical localization of D1 and D2 dopamine receptors in the basal ganglia of the rat: light and electron microscopy. Neuroscience 1995; 65: 709–730.

    Article  CAS  PubMed  Google Scholar 

  62. Wang HY, Undie AS, Friedman E . 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 1995; 48: 988–994.

    CAS  PubMed  Google Scholar 

  63. Mannoury la Cour C, Vidal S, Pasteau V, Cussac D, Millan MJ . Dopamine D1 receptor coupling to Gs/olf and Gq in rat striatum and cortex: a scintillation proximity assay (SPA)/antibody-capture characterization of benzazepine agonists. Neuropharmacology 2007; 52: 1003–1014.

    Article  CAS  PubMed  Google Scholar 

  64. Wadenberg ML, Kapur S, Soliman A, Jones C, Vaccarino F . Dopamine D2 receptor occupancy predicts catalepsy and the suppression of conditioned avoidance response behavior in rats. Psychopharmacology 2000; 150: 422–429.

    Article  CAS  PubMed  Google Scholar 

  65. Surmeier DJ, Song WJ, Yan Z . Coordinated expression of dopamine receptors in neostriatal medium spiny neurons. J Neurosci 1996; 16: 6579–6591.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Matamales M, Bertran-Gonzalez J, Salomon L, Degos B, Deniau JM, Valjent E et al. Striatal medium-sized spiny neurons: identification by nuclear staining and study of neuronal subpopulations in BAC transgenic mice. PloS One 2009; 4: e4770.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Cahill E, Pascoli V, Trifilieff P, Savoldi D, Kappes V, Luscher C et al. D1R/GluN1 complexes in the striatum integrate dopamine and glutamate signalling to control synaptic plasticity and cocaine-induced responses. Mol Psychiatry 2014; 19: 1295–1304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Perreault ML, Hasbi A, Alijaniaram M, O'Dowd BF, George SR . Reduced striatal dopamine D1-D2 receptor heteromer expression and behavioural subsensitivity in juvenile rats. Neuroscience 2012; 225: 130–139.

    Article  CAS  PubMed  Google Scholar 

  69. Perreault ML, Hasbi A, O'Dowd BF, George SR . Heteromeric dopamine receptor signaling complexes: emerging neurobiology and disease relevance. Neuropsychopharmacology 2014; 39: 156–168.

    Article  CAS  PubMed  Google Scholar 

  70. Rosell DR, Zaluda LC, McClure MM, Perez-Rodriguez MM, Strike KS, Barch DM et al. Effects of the D dopamine receptor agonist dihydrexidine (DAR-0100A) on working memory in schizotypal personality disorder. Neuropsychopharmacology advance online publication, 30 July 2014; doi:10.1038/npp.2014.192 (e-pub ahead of print).

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Acknowledgements

This work was supported by NIH grants RO1MH086629 (GDS), F31DA029499 (to ALF), TL1 RR024158-04 (to HY), K05DA022413 and R01MH54137 (to JAJ), RO1MH093672 (to CK), R01NS078291 (to RJC), a Research scientist award from the Research Foundation for Mental Hygiene (to PT) and the Lieber Center for Schizophrenia Research and Treatment. Behavioral work was performed at the Vanderbilt Mouse Neurobehavioral Core, which is supported in part by P30HD15052. We thank Dr Celine Gales (Institut National de la Santé et de la Recherche Médicale, Toulouse, France) and Dr Nevin Lambert (Georgia Health Sciences University, Augusta, Georgia) for kindly sharing Rluc and Venus fusion G protein constructs, Dr Stefan Offermanns (University of Heidelberg, Germany) for supplying the Gαq mutant line and Dr Nicole Calakos (Duke University) for the Drd1a-tdTomato reporter line. We also thank Matt Buendia, Heather Durai and Dr John Allison for excellent technical assistance.

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Author notes

  1. H Yano

    Present address: 12Current address: National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.,

  2. A L Frederick, H Yano, P Trifilieff, G D Stanwood and J A Javitch: These authors contributed equally to this work.

Authors and Affiliations

  1. Neuroscience Graduate Program, Vanderbilt University School of Medicine, Nashville, TN, USA

    A L Frederick

  2. Departments of Psychiatry and Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY, USA

    H Yano, D Biezonski, J Mészáros, E Urizar, C Kellendonk & J A Javitch

  3. Nutrition and Integrative Neurobiology, INRA UMR 1286,

    P Trifilieff

  4. University of Bordeaux, Bordeaux, France

    P Trifilieff

  5. Department of Neuroscience, Columbia University, New York, NY, USA

    P Trifilieff & H D Vishwasrao

  6. Molecular Neuropharmacology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

    D R Sibley

  7. Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY, USA

    C Kellendonk & J A Javitch

  8. Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA, USA

    K C Sonntag

  9. Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA

    D L Graham & G D Stanwood

  10. Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA

    R J Colbran

  11. Vanderbilt Kennedy Center and Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, TN, USA

    R J Colbran & G D Stanwood

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  1. A L Frederick
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Frederick, A., Yano, H., Trifilieff, P. et al. Evidence against dopamine D1/D2 receptor heteromers. Mol Psychiatry 20, 1373–1385 (2015). https://doi.org/10.1038/mp.2014.166

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