Individual differences in dopamine D2 receptor availability correlate with reward valuation

  • Linh C. DangEmail author
  • Gregory R. Samanez-Larkin
  • Jaime J. Castrellon
  • Scott F. Perkins
  • Ronald L. Cowan
  • David H. Zald


Reward valuation, which underlies all value-based decision-making, has been associated with dopamine function in many studies of nonhuman animals, but there is relatively less direct evidence for an association in humans. Here, we measured dopamine D2 receptor (DRD2) availability in vivo in humans to examine relations between individual differences in dopamine receptor availability and neural activity associated with a measure of reward valuation, expected value (i.e., the product of reward magnitude and the probability of obtaining the reward). Fourteen healthy adult subjects underwent PET with [18F]fallypride, a radiotracer with strong affinity for DRD2, and fMRI (on a separate day) while performing a reward valuation task. [18F]fallypride binding potential, reflecting DRD2 availability, in the midbrain correlated positively with neural activity associated with expected value, specifically in the left ventral striatum/caudate. The present results provide in vivo evidence from humans showing midbrain dopamine characteristics are associated with reward valuation.


Reward valuation Dopamine Ventral striatum Midbrain 



This work was supported by the National Institute on Aging (R01AG044838 to DHZ, R00AG042596 to G.R.S.L.), the National Institute on Drug Abuse (F32DA036979 to L.C.D.), and the Vanderbilt Institute for Clinical and Translational Research which receives funding from the National Center for Advancing Translational Sciences. Funding institutes were not involved in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the article for publication.

Compliance with ethical standards

Conflict of interest



  1. Abler, B., Walter, H., Erk, S., Kammerer, H., & Spitzer, M. (2006). Prediction error as a linear function of reward probability is coded in human nucleus accumbens. NeuroImage, 31, 790–795.CrossRefPubMedGoogle Scholar
  2. Andersson, J., Jenkinson, M., & Smith, S. (2007). Non-linear registration aka spatial normalisation (FMRIB Technial Report TR07JA2). Retrieved from
  3. Aron, A. R., Gluck, M. A., & Poldrack, R. A. (2006). Long-term test–retest reliability of functional MRI in a classification learning task. NeuroImage, 29, 1000–1006.CrossRefPubMedGoogle Scholar
  4. Bartra, O., McGuire, J. T., & Kable, J. W. (2013). The valuation system: A coordinate-based meta-analysis of BOLD fMRI experiments examining neural correlates of subjective value. NeuroImage, 76, 412–427.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Brody, A. L., Olmstead, R. E., London, E. D., Farahi, J., Meyer, J. H., Grossman, P., … Mandelkern, M. A. (2004). Smoking-induced ventral striatum dopamine release. American Journal of Psychiatry, 161, 1211–1218.CrossRefPubMedGoogle Scholar
  6. Buckholtz, J. W., Treadway, M. T., Cowan, R. L., Woodward, N. D., Benning, S. D., Li, R., Ansari, M. S.,… Zald, D. H. (2010a). Mesolimbic dopamine reward system hypersensitivity in individuals with psychopathic traits. Nature Neuroscience, 13, 419–421.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Buckholtz, J. W., Treadway, M. T., Cowan, R. L., Woodward, N. D., Li, R., Ansari, M. S.,… Zald, D. H. (2010b). Dopaminergic network differences in human impulsivity. Science, 329, 532. doi: CrossRefPubMedPubMedCentralGoogle Scholar
  8. Camps, M., Cortes, R., Gueye, B., Probst, A., & Palacios, J. M. (1989). Dopamine receptors in human brain: Autoradiographic distribution of D2 sites. Neuroscience, 28, 275–290.CrossRefPubMedGoogle Scholar
  9. Cannon, D.M., Klaver, J. M., Peck, S. A., Rallis-Voak, D., Erickson, K., & Drevets, W. C. (2009). Dopamine type-1 receptor binding in major depressive disorder assessed using positron emission tomography and [11C]NNC-112. Neuropsychopharmacology, 34, 1277–1287.CrossRefPubMedGoogle Scholar
  10. Cooper, J. R., Bloom, F. E., & Roth, R. H. (2003). The biochemical basis of neuropharmacology (8th ed.). Oxford, UK: Oxford University Press.Google Scholar
  11. Cromwell, H. C., & Schultz, W. (2003). Effects of expectations for different reward magnitudes on neuronal activity in primate striatum. Journal of Neurophysiology, 89, 2823–2838.CrossRefPubMedGoogle Scholar
  12. Dang, L. C., O’Neil, J. P., & Jagust, W. J. (2012a). Dopamine supports coupling of attention-related networks. Journal of Neuroscience, 32, 9582–9587.CrossRefPubMedGoogle Scholar
  13. Dang, L. C., O’Neil, J. P., & Jagust, W. J. (2012b). Genetic effects on behavior are mediated by neurotransmitters and large-scale neural networks. NeuroImage, 66C, 203–214. doi: Google Scholar
  14. D’Ardenne, K., McClure, S. M., Nystrom, L. E., & Cohen, J. D. (2008). BOLD responses reflecting dopaminergic signals in the human ventral tegmental area. Science, 319, 1264–1267.CrossRefPubMedGoogle Scholar
  15. Davis, C., Levitan, R. D., Kaplan, A. S., Carter, J., Reid, C., Curtis, C.,... Kennedy, J. L. (2008). Reward sensitivity and the D2 dopamine receptor gene: A case-control study of binge eating disorder. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 32, 620–628.CrossRefGoogle Scholar
  16. Der-Avakian, A., & Markou, A. (2012). The neurobiology of anhedonia and other reward-related deficits. Trends in Neuroscience, 35, 68–77.CrossRefGoogle Scholar
  17. Diekhof, E. K., Kaps, L., Falkai, P., & Gruber, O. (2012). The role of the human ventral striatum and the medial orbitofrontal cortex in the representation of reward magnitude—An activation likelihood estimation meta-analysis of neuroimaging studies of passive reward expectancy and outcome processing. Neuropsychologia, 50, 1252–1266.CrossRefPubMedGoogle Scholar
  18. Dreher, J. C., Meyer-Lindenberg, A., Kohn, P., & Berman, K. F. (2008). Age-related changes in midbrain dopaminergic regulation of the human reward system. Proceedings of the National Academy of Sciences of the United States of America, 105, 15106–15111.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Eklund, A., Nichols, T. E., & Knutsson, H. (2016). Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates. Proceedings of the National Academy of Sciences of the United States of America, 113, 7900–7905.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Fiorillo, C. D., Tobler, P. N., & Schultz, W. (2003). Discrete coding of reward probability and uncertainty by dopamine neurons. Science, 299, 1898–1902.CrossRefPubMedGoogle Scholar
  21. First, M.B., Spitzer, R.L., Gibbon, M., & Williams, J.B.W., (1997). Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). American Psychiatric Publishing, Inc., Washington, D.C.Google Scholar
  22. Gan, J. O., Walton, M. E., & Phillips, P. E. (2010). Dissociable cost and benefit encoding of future rewards by mesolimbic dopamine. Nature Neuroscience, 13, 25–27.CrossRefPubMedGoogle Scholar
  23. Glimcher, P. W., & Fehr, E. (2013). Neuroeconomics: Decision making and the brain (2nd ed.). San Diengo, CA: Academic Press.Google Scholar
  24. Gluskin, B. S., & Mickey, B. J. (2016). Genetic variation and dopamine D2 receptor availability: A systematic review and meta-analysis of human in vivo molecular imaging studies. Translational Psychiatry, 6, e747. doi: CrossRefPubMedPubMedCentralGoogle Scholar
  25. Grace, A. A. (2000). The tonic/phasic model of dopamine system regulation and its implications for understanding alcohol and psychostimulant craving. Addiction, 95(Suppl. 2), S119–S128.CrossRefPubMedGoogle Scholar
  26. Greve, D. N., & Fischl, B. (2009). Accurate and robust brain image alignment using boundary-based registration. NeuroImage, 48, 63–72.CrossRefPubMedPubMedCentralGoogle Scholar
  27. Hare, T. A., O’Doherty, J., Camerer, C. F., Schultz, W., & Rangel, A. (2008). Dissociating the role of the orbitofrontal cortex and the striatum in the computation of goal values and prediction errors. Journal of Neuroscience, 28, 5623–5630.CrossRefPubMedGoogle Scholar
  28. Juckel, G., Schlagenhauf, F., Koslowski, M., Wustenberg, T., Villringer, A., Knutson, B.,… Heinz, A. (2006). Dysfunction of ventral striatal reward prediction in schizophrenia. NeuroImage, 29, 409–416.CrossRefPubMedGoogle Scholar
  29. Kirsch, P., Reuter, M., Mier, D., Lonsdorf, T., Stark, R., Gallhofer, B.,… Hennig, J. (2006). Imaging gene-substance interactions: The effect of the DRD2 TaqIA polymorphism and the dopamine agonist bromocriptine on the brain activation during the anticipation of reward. Neuroscience Letters, 405, 196–201.CrossRefPubMedGoogle Scholar
  30. Knutson, B., Adams, C. M., Fong, G. W., & Hommer, D. (2001). Anticipation of increasing monetary reward selectively recruits nucleus accumbens. Journal of Neuroscience, 21, RC159. doi: CrossRefPubMedGoogle Scholar
  31. Knutson, B., & Cooper, J. C. (2005). Functional magnetic resonance imaging of reward prediction. Current Opinion in Neurology, 18, 411–417.CrossRefPubMedGoogle Scholar
  32. Laruelle, M., Gelernter, J., & Innis, R. B. (1998). D2 receptors binding potential is not affected by Taq1 polymorphism at the D2 receptor gene. Molecular Psychiatry, 3, 261–265.CrossRefPubMedGoogle Scholar
  33. Linnet, J., Peterson, E., Doudet, D. J., Gjedde, A., & Moller, A. (2010). Dopamine release in ventral striatum of pathological gamblers losing money. Acta Psychiatrica Scandinavica, 122, 326–333.CrossRefPubMedGoogle Scholar
  34. Martin-Soelch, C., Szczepanik, J., Nugent, A., Barhaghi, K., Rallis, D., Herscovitch, P., … Drevets, W. C. (2011). Lateralization and gender differences in the dopaminergic response to unpredictable reward in the human ventral striatum. European Journal of Neuroscience, 33, 1706–1715.CrossRefPubMedGoogle Scholar
  35. Mawlawi, O., Martinez, D., Slifstein, M., Broft, A., Chatterjee, R., Hwang, D. R., … Laruelle, M. (2001). Imaging human mesolimbic dopamine transmission with positron emission tomography: I. Accuracy and precision of D2 receptor parameter measurements in ventral striatum. Journal of Cerebral Blood Flow & Metabolism, 21, 1034–1057.CrossRefGoogle Scholar
  36. McClure, S.M., Berns, G. S., & Montague, P. R. (2003). Temporal prediction errors in a passive learning task activate human striatum. Neuron, 38, 339–346.CrossRefPubMedGoogle Scholar
  37. McClure, S. M., York, M. K., & Montague, P. R. (2004). The neural substrates of reward processing in humans: The modern role of FMRI. Neuroscientist, 10, 260–268.CrossRefPubMedGoogle Scholar
  38. Menza, M. A., Mark, M. H., Burn, D. J., & Brooks, D. J. (1995). Personality correlates of [18F]dopa striatal uptake: Results of positron-emission tomography in Parkinson’s disease. Journal of Neuropsychiatry and Clinical Neurosciences, 7, 176–179.CrossRefPubMedGoogle Scholar
  39. Monchi, O., Ko, J. H., & Strafella, A. P. (2006). Striatal dopamine release during performance of executive functions: A [11C] raclopride PET study. NeuroImage, 33, 907–912.CrossRefPubMedPubMedCentralGoogle Scholar
  40. Montague, P. R., King-Casas, B., & Cohen, J. D. (2006). Imaging valuation models in human choice. Annual Review of Neuroscience, 29, 417–448.CrossRefPubMedGoogle Scholar
  41. Mukherjee, J., Christian, B. T., Dunigan, K. A., Shi, B., Narayanan, T. K., Satter, M., & Mantil, J. (2002). Brain imaging of 18F-fallypride in normal volunteers: Blood analysis, distribution, test-retest studies, and preliminary assessment of sensitivity to aging effects on dopamine D-2/D-3 receptors. Synapse, 46, 170–188.CrossRefPubMedGoogle Scholar
  42. Mukherjee, J., Yang, Z. Y., Das, M. K., & Brown, T. (1995). Fluorinated benzamide neuroleptics—III. Development of (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-[18F]fluoropropyl)-2, 3-dimethoxybenzamide as an improved dopamine D-2 receptor tracer. Nuclear Medicine and Biology, 22, 283–296.CrossRefPubMedGoogle Scholar
  43. Niv, Y. (2009). Reinforcement learning in the brain. Journal of Mathematical Psychology, 53, 139–154.CrossRefGoogle Scholar
  44. O’Doherty, J. P. (2004). Reward representations and reward-related learning in the human brain: Insights from neuroimaging. Current Opinion in Neurobiology, 14, 769–776.CrossRefPubMedGoogle Scholar
  45. O’Doherty, J. P., Dayan, P., Friston, K., Critchley, H., & Dolan, R. J. (2003). Temporal difference models and reward-related learning in the human brain. Neuron, 38, 329–337.CrossRefPubMedGoogle Scholar
  46. O’Donnell, P., & Grace, A. A. (1994). Tonic D2-mediated attenuation of cortical excitation in nucleus accumbens neurons recorded in vitro. Brain Research, 634, 105–112.CrossRefPubMedGoogle Scholar
  47. Pagnoni, G., Zink, C. F., Montague, P. R., & Berns, G. S. (2002). Activity in human ventral striatum locked to errors of reward prediction. Nature Neuroscience, 5, 97–98.CrossRefPubMedGoogle Scholar
  48. Pappata, S., Dehaene, S., Poline, J. B., Gregoire, M. C., Jobert, A., Delforge, J., … Syrota, A. (2002). In vivo detection of striatal dopamine release during reward: A PET study with [11C]raclopride and a single dynamic scan approach. NeuroImage, 16, 1015–1027.CrossRefPubMedGoogle Scholar
  49. Plassmann, H., O’Doherty, J., & Rangel, A. (2007). Orbitofrontal cortex encodes willingness to pay in everyday economic transactions. Journal of Neuroscience, 27, 9984–9988.CrossRefPubMedGoogle Scholar
  50. Platt, M. L., & Huettel, S. A. (2008). Risky business: The neuroeconomics of decision making under uncertainty. Nature Neuroscience, 11, 398–403.CrossRefPubMedPubMedCentralGoogle Scholar
  51. Roesch, M. R., Takahashi, Y., Gugsa, N., Bissonette, G. B., & Schoenbaum, G. (2007). Previous cocaine exposure makes rats hypersensitive to both delay and reward magnitude. Journal of Neuroscience, 27, 245–250.CrossRefPubMedGoogle Scholar
  52. Rolls, E. T., McCabe, C., & Redoute, J. (2008). Expected value, reward outcome, and temporal difference error representations in a probabilistic decision task. Cerebral Cortex, 18, 652–663.CrossRefPubMedGoogle Scholar
  53. Samejima, K., Ueda, Y., Doya, K., & Kimura, M. (2005). Representation of action-specific reward values in the striatum. Science, 310, 1337–1340.CrossRefPubMedGoogle Scholar
  54. Schott, B. H., Minuzzi, L., Krebs, R. M., Elmenhorst, D., Lang, M., ... Bauer, A. (2008). Mesolimbic functional magnetic resonance imaging activations during reward anticipation correlate with reward-related ventral striatal dopamine release. Journal of Neuroscience, 28, 14311–14319.CrossRefPubMedGoogle Scholar
  55. Schultz, W. (2010). Dopamine signals for reward value and risk: Basic and recent data. Behavioral and Brain Functions, 6, 24.CrossRefPubMedGoogle Scholar
  56. Schultz, W., Apicella, P., Scarnati, E., & Ljungberg, T. (1992). Neuronal activity in monkey ventral striatum related to the expectation of reward. Journal of Neuroscience, 12, 4595–4610.CrossRefPubMedGoogle Scholar
  57. Schwartz, W. J., Sharp, F. R., Gunn, R. H., & Evarts, E. V. (1976). Lesions of ascending dopaminergic pathways decrease forebrain glucose uptake. Nature, 261, 155–157.CrossRefPubMedGoogle Scholar
  58. Siessmeier, T., Zhou, Y., Buchholz, H. G., Landvogt, C., Vernaleken, I., Piel, M., … Bartenstein, P. (2005). Parametric mapping of binding in human brain of D2 receptor ligands of different affinities. Journal of Nuclear Medicine, 46, 964–972.PubMedGoogle Scholar
  59. Smith, C. T., Dang, L. C., Buckholtz, J. W., Tetreault, A. M., Cowan, R. L., Kessler, R. M., & Zald, D. (2017). The impact of common dopamine D2 receptor gene polymorphisms on D2/3 receptor availability: C957T as a key determinant in putamen and ventral striatum. Translational Psychiatry. doi:
  60. Stice, E., Yokum, S., Bohon, C., Marti, N., & Smolen, A. (2010). Reward circuitry responsivity to food predicts future increases in body mass: Moderating effects of DRD2 and DRD4. NeuroImage, 50, 1618–1625.CrossRefPubMedPubMedCentralGoogle Scholar
  61. Tobler, P. N., Fiorillo, C. D., & Schultz, W. (2005). Adaptive coding of reward value by dopamine neurons. Science, 307, 1642–1645.CrossRefPubMedGoogle Scholar
  62. Tomer, R., & Aharon-Peretz, J. (2004). Novelty seeking and harm avoidance in Parkinson’s disease: Effects of asymmetric dopamine deficiency. Journal of Neurology, Neurosurgery, & Psychiatry, 75, 972–975.CrossRefGoogle Scholar
  63. Tomer, R., Goldstein, R. Z., Wang, G. J., Wong, C., & Volkow, N. D. (2008). Incentive motivation is associated with striatal dopamine asymmetry. Biological Psychology, 77, 98–101.CrossRefPubMedGoogle Scholar
  64. Tomer, R., Slagter, H. A., Christian, B. T., Fox, A. S., King, C. R., Murali, D., … Davidson, R. J. (2014). Love to win or hate to lose? Asymmetry of dopamine D2 receptor binding predicts sensitivity to reward versus punishment. Journal of Cognitive Neuroscience, 26, 1039–1048.CrossRefPubMedGoogle Scholar
  65. Tricomi, E., & Lempert, K. M. (2015). Value and probability coding in a feedback-based learning task utilizing food rewards. Journal of Neurophysiology, 113, 4–13.CrossRefPubMedGoogle Scholar
  66. Wolf, M. E., & Roth, R. H. (1990). Autoreceptor regulation of dopamine synthesis. Annals of the New York Academy of Sciences, 604, 323–343.CrossRefPubMedGoogle Scholar
  67. Zald, D. H., Boileau, I., El-Dearedy, W., Gunn, R., McGlone, F., Dichter, G. S., & Dagher, A. (2004). Dopamine transmission in the human striatum during monetary reward tasks. Journal of Neuroscience, 24, 4105–4112.CrossRefPubMedGoogle Scholar
  68. Zald, D. H., Cowan, R. L., Riccardi, P., Baldwin, R. M., Ansari, M. S., ... Kessler, R. M. (2008). Midbrain dopamine receptor availability is inversely associated with novelty-seeking traits in humans. Journal of Neuroscience, 28, 14372–14378.CrossRefPubMedGoogle Scholar

Copyright information

© Psychonomic Society, Inc. 2018

Authors and Affiliations

  • Linh C. Dang
    • 1
    Email author
  • Gregory R. Samanez-Larkin
    • 2
  • Jaime J. Castrellon
    • 2
  • Scott F. Perkins
    • 1
  • Ronald L. Cowan
    • 3
    • 4
  • David H. Zald
    • 1
    • 3
  1. 1.Department of PsychologyVanderbilt UniversityNashvilleUSA
  2. 2.Department of Psychology and NeuroscienceDuke UniversityDurhamUSA
  3. 3.Department of Psychiatry and Behavioral SciencesVanderbilt University School of MedicineNashvilleUSA
  4. 4.Department of Radiology and Radiological SciencesVanderbilt University Medical CenterNashvilleUSA

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