Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Scientific Reports
  • View all journals
  • Search
  • My Account Login
  • Content Explore content
  • About the journal
  • Publish with us
  • Sign up for alerts
  • RSS feed
  1. nature
  2. scientific reports
  3. articles
  4. article
The effect of dopamine D2-like receptor blockade on human motor performance and skill acquisition
Download PDF
Download PDF
  • Article
  • Open access
  • Published: 20 January 2026

The effect of dopamine D2-like receptor blockade on human motor performance and skill acquisition

  • Eleanor M. Taylor1 na1,
  • Dylan Curtin1 na1,
  • Trevor T.-J. Chong1,2,3,
  • Mark A. Bellgrove1 &
  • …
  • James P. Coxon1 

Scientific Reports , Article number:  (2026) Cite this article

  • 504 Accesses

  • Metrics details

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Cognitive neuroscience
  • Human behaviour
  • Learning and memory

Abstract

Dopamine signalling supports motor skill learning in a variety of ways, including through an effect on cortical and striatal plasticity. One neuromodulator that has been consistently linked to motor skill learning is dopamine. However, the specific role of dopamine D2-like receptor in the acquisition and consolidation stages of motor learning remains unclear. The aim of this study was to examine the effect of a selective D2-like receptor antagonist on human motor skill acquisition and consolidation. In this randomised, double-blind, placebo-controlled design, healthy adult men and women (N = 23) completed a sequential motor skill learning task after taking either sulpiride (800 mg) or placebo. A 20-minute bout of high-intensity interval cycling exercise was included to enhance learning effects and counteract potentially confounding sedative effects of sulpiride. Results showed that sulpiride reduced performance during motor skill acquisition relative to placebo in the first session, however this difference was abolished at the subsequent retention test. Sulpiride did not reduce consolidation of learning as expected, however it led to a reduction in speed of execution relative to placebo. Our results provide preliminary evidence of a causal relationship between neuromodulation at the dopamine D2-like receptor and motor performance during early acquisition of a novel motor skill. These results may have functional relevance in motor rehabilitation as reduced dopamine transmission can impact performance during initial acquisition and slow subsequent performance of the skill.

Data availability

Behavioural data are available upon request by contacting the corresponding author (J.P.C).

References

  1. Krakauer, J. W., Hadjiosif, A. M., Xu, J., Wong, A. L. & Haith, A. M. Motor learning. Compr. Physiol. 9, 613–663. https://doi.org/10.1002/cphy.c170043 (2019).

    Google Scholar 

  2. Krakauer, J. W. Motor learning: its relevance to stroke recovery and neurorehabilitation. Curr. Opin. Neurol. 19, 84–90. https://doi.org/10.1097/01.wco.0000200544.29915.cc (2006).

    Google Scholar 

  3. Dayan, E. & Cohen, L. G. Neuroplasticity subserving motor skill learning. Neuron 72, 443–454. https://doi.org/10.1016/j.neuron.2011.10.008 (2011).

    Google Scholar 

  4. Coddington, L. T. & Dudman, J. T. Learning from action: reconsidering movement signaling in midbrain dopamine neuron activity. Neuron 104, 63–77. https://doi.org/10.1016/j.neuron.2019.08.036 (2019).

    Google Scholar 

  5. Robbins, T. W. & Everitt, B. J. Functions of dopamine in the dorsal and ventral striatum. Seminars Neurosci. 4, 119–127. https://doi.org/10.1016/1044-5765(92)90010-Y (1992).

    Google Scholar 

  6. Schultz, W. Neuronal reward and decision signals: from theories to data. Physiol. Rev. 95, 853–951. https://doi.org/10.1152/physrev.00023.2014 (2015).

    Google Scholar 

  7. Albin, R. L., Young, A. B. & Penney, J. B. The functional anatomy of basal ganglia disorders. Trends Neurosci. 12, 366–375. https://doi.org/10.1016/0166-2236(89)90074-x (1989).

    Google Scholar 

  8. Alexander, G. E., DeLong, M. R. & Strick, P. L. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu. Rev. Neurosci. 9, 357–381. https://doi.org/10.1146/annurev.ne.09.030186.002041 (1986).

    Google Scholar 

  9. Dreyer, J. K., Herrik, K. F., Berg, R. W. & Hounsgaard, J. D. Influence of phasic and tonic dopamine release on receptor activation. J. Neurosci. 30, 14273–14283. https://doi.org/10.1523/jneurosci.1894-10.2010 (2010).

    Google Scholar 

  10. Wiecki, T. V. & Frank, M. J. Neurocomputational models of motor and cognitive deficits in parkinson’s disease. Prog Brain Res. 183, 275–297. https://doi.org/10.1016/s0079-6123(10)83014-6 (2010).

    Google Scholar 

  11. Hosp, J. A., Pekanovic, A., Rioult-Pedotti, M. S. & Luft, A. R. Dopaminergic projections from midbrain to primary motor cortex mediate motor skill learning. J. Neurosci. 31, 2481–2487 (2011).

    Google Scholar 

  12. Molina-Luna, K. et al. Dopamine in motor cortex is necessary for skill learning and synaptic plasticity. PLoS One. 4, e7082. https://doi.org/10.1371/journal.pone.0007082 (2009).

    Google Scholar 

  13. Rioult-Pedotti, M. S., Pekanovic, A., Atiemo, C. O., Marshall, J. & Luft, A. R. Dopamine promotes motor cortex plasticity and motor skill learning via PLC activation. PLoS One. 10, e0124986. https://doi.org/10.1371/journal.pone.0124986 (2015).

    Google Scholar 

  14. Nakamura, T. et al. Distinct motor impairments of dopamine D1 and D2 receptor knockout mice revealed by three types of motor behavior. Front. Integr. Neurosci. 8, 56. https://doi.org/10.3389/fnint.2014.00056 (2014).

    Google Scholar 

  15. Sommer, W. H., Costa, R. M. & Hansson, A. C. Dopamine systems adaptation during acquisition and consolidation of a skill. Front. Integr. Neurosci. 8, 87 (2014).

    Google Scholar 

  16. Yin, H. H. et al. Dynamic reorganization of striatal circuits during the acquisition and consolidation of a skill. Nat. Neurosci. 12, 333–341. https://doi.org/10.1038/nn.2261 (2009).

    Google Scholar 

  17. Debas, K. et al. Off-line consolidation of motor sequence learning results in greater integration within a cortico-striatal functional network. Neuroimage 99, 50–58. https://doi.org/10.1016/j.neuroimage.2014.05.022 (2014).

    Google Scholar 

  18. Doyon, J., Gabitov, E., Vahdat, S., Lungu, O. & Boutin, A. Current issues related to motor sequence learning in humans. Curr. Opin. Behav. Sci. 20, 89–97. https://doi.org/10.1016/j.cobeha.2017.11.012 (2018).

    Google Scholar 

  19. Kishore, A., Joseph, T., Velayudhan, B., Popa, T. & Meunier, S. Early, severe and bilateral loss of LTP and LTD-like plasticity in motor cortex (M1) in de Novo parkinson’s disease. Clin. Neurophysiol. 123, 822–828. https://doi.org/10.1016/j.clinph.2011.06.034 (2012).

    Google Scholar 

  20. Suppa, A. et al. Lack of LTP-like plasticity in primary motor cortex in parkinson’s disease. Exp. Neurol. 227, 296–301. https://doi.org/10.1016/j.expneurol.2010.11.020 (2011).

    Google Scholar 

  21. Ueki, Y. et al. Altered plasticity of the human motor cortex in parkinson’s disease. Ann. Neurol. 59, 60–71. https://doi.org/10.1002/ana.20692 (2006).

    Google Scholar 

  22. Marinelli, L., Quartarone, A., Hallett, M., Frazzitta, G. & Ghilardi, M. F. The many facets of motor learning and their relevance for parkinson’s disease. Clin. Neurophysiol. 128, 1127–1141. https://doi.org/10.1016/j.clinph.2017.03.042 (2017).

    Google Scholar 

  23. Ueda, N. et al. Relationship between motor learning and gambling propensity in parkinson’s disease. J. Clin. Exp. Neuropsychol. 44, 50–61. https://doi.org/10.1080/13803395.2022.2083083 (2022).

    Google Scholar 

  24. Dan, X., King, B. R., Doyon, J. & Chan, P. Motor sequence learning and consolidation in unilateral de Novo patients with parkinson’s disease. PLoS One. 10, e0134291. https://doi.org/10.1371/journal.pone.0134291 (2015).

    Google Scholar 

  25. Lahlou, S., Gabitov, E., Owen, L., Shohamy, D. & Sharp, M. Preserved motor memory in parkinson’s disease. Neuropsychologia 167, 108161. https://doi.org/10.1016/j.neuropsychologia.2022.108161 (2022).

    Google Scholar 

  26. Noohi, F. et al. Interactive effects of age and multi-gene profile on motor learning and sensorimotor adaptation. Neuropsychologia 84, 222–234. https://doi.org/10.1016/j.neuropsychologia.2016.02.021 (2016).

    Google Scholar 

  27. Schuck, N. W. et al. Effects of aging and dopamine genotypes on the emergence of explicit memory during sequence learning. Neuropsychologia 51, 2757–2769. https://doi.org/10.1016/j.neuropsychologia.2013.09.009 (2013).

    Google Scholar 

  28. Noohi, F. et al. Association of COMT val158met and DRD2 G > T genetic polymorphisms with individual differences in motor learning and performance in female young adults. J. Neurophysiol. 111, 628–640. https://doi.org/10.1152/jn.00457.2013 (2014).

    Google Scholar 

  29. Baetu, I., Burns, N. R., Urry, K., Barbante, G. G. & Pitcher, J. B. Commonly-occurring polymorphisms in the COMT, DRD1 and DRD2 genes influence different aspects of motor sequence learning in humans. Neurobiol. Learn. Mem. 125, 176–188. https://doi.org/10.1016/j.nlm.2015.09.009 (2015).

    Google Scholar 

  30. Monte-Silva, K. et al. D2 receptor block abolishes θ burst stimulation-induced neuroplasticity in the human motor cortex. Neuropsychopharmacology: Official Publication Am. Coll. Neuropsychopharmacol. 36, 2097–2102. https://doi.org/10.1038/npp.2011.100 (2011).

    Google Scholar 

  31. Meintzschel, F. & Ziemann, U. Modification of practice-dependent plasticity in human motor cortex by neuromodulators. Cereb. Cortex. 16, 1106–1115. https://doi.org/10.1093/cercor/bhj052 (2006).

    Google Scholar 

  32. Floel, A. et al. Dopaminergic influences on formation of a motor memory. Ann. Neurol. 58, 121–130. https://doi.org/10.1002/ana.20536 (2005).

    Google Scholar 

  33. Vaillancourt, D. E., Schonfeld, D., Kwak, Y., Bohnen, N. I. & Seidler, R. Dopamine overdose hypothesis: evidence and clinical implications. Mov. Disord. 28, 1920–1929. https://doi.org/10.1002/mds.25687 (2013).

    Google Scholar 

  34. Hattori, S., Naoi, M. & Nishino, H. Striatal dopamine turnover during treadmill running in the rat: relation to the speed of running. Brain Res. Bull. 35, 41–49. https://doi.org/10.1016/0361-9230(94)90214-3 (1994).

    Google Scholar 

  35. Sacheli, M. A. et al. Exercise increases caudate dopamine release and ventral striatal activation in parkinson’s disease. Mov. Disord. 34, 1891–1900. https://doi.org/10.1002/mds.27865 (2019).

    Google Scholar 

  36. Wanner, P., Cheng, F. H. & Steib, S. Effects of acute cardiovascular exercise on motor memory encoding and consolidation: a systematic review with meta-analysis. Neurosci. Biobehav Rev. 116, 365–381. https://doi.org/10.1016/j.neubiorev.2020.06.018 (2020).

    Google Scholar 

  37. Christiansen, L. et al. The beneficial effect of acute exercise on motor memory consolidation is modulated by dopaminergic gene profile. J. Clin. Med. 8, 578 (2019).

    Google Scholar 

  38. Mang, C. S. et al. Exploring genetic influences underlying acute aerobic exercise effects on motor learning. Sci. Rep. 7, 12123–12123. https://doi.org/10.1038/s41598-017-12422-3 (2017).

    Google Scholar 

  39. Curtin, D., Taylor, E. M., Bellgrove, M. A., Chong, T. T. & Coxon, J. P. D2 receptor Blockade eliminates exercise-induced changes in cortical Inhibition and excitation. Brain Stimul. 16, 727–733. https://doi.org/10.1016/j.brs.2023.04.019 (2023).

    Google Scholar 

  40. Curtin, D., Taylor, E. M., Bellgrove, M. A., Chong, T. T. & Coxon, J. P. Dopamine D2 receptor modulates exercise related effect on cortical Excitation/Inhibition and motor skill acquisition. J. Neurosci. 44 https://doi.org/10.1523/JNEUROSCI.2028-23.2024 (2024).

  41. Miyamoto, S., Duncan, G. E., Marx, C. E. & Lieberman, J. A. Treatments for schizophrenia: a critical review of Pharmacology and mechanisms of action of antipsychotic drugs. Mol. Psychiatry. 10, 79–104. https://doi.org/10.1038/sj.mp.4001556 (2005).

    Google Scholar 

  42. Reis, J. et al. Noninvasive cortical stimulation enhances motor skill acquisition over multiple days through an effect on consolidation. Proc. Natl. Acad. Sci. U S A. 106, 1590–1595. https://doi.org/10.1073/pnas.0805413106 (2009).

    Google Scholar 

  43. Luft, A. R. & Buitrago, M. M. Stages of motor skill learning. Mol. Neurobiol. 32, 205–216. https://doi.org/10.1385/mn:32:3 (2005).

    Google Scholar 

  44. Stavrinos, E. L. & Coxon, J. P. High-intensity interval exercise promotes motor cortex disinhibition and early motor skill consolidation. J. Cogn. Neurosci. 29, 593–604. https://doi.org/10.1162/jocn_a_01078 (2017).

    Google Scholar 

  45. Dietrich, A. & Audiffren, M. The reticular-activating hypofrontality (RAH) model of acute exercise. Neurosci. Biobehav Rev. 35, 1305–1325. https://doi.org/10.1016/j.neubiorev.2011.02.001 (2011).

    Google Scholar 

  46. Loy, B. D., Dishman, R. K. & J., O. C. P. & and The effect of a single bout of exercise on energy and fatigue states: a systematic review and meta-analysis. Fatigue: Biomed. Health Behav. 1, 223–242. https://doi.org/10.1080/21641846.2013.843266 (2013).

    Google Scholar 

  47. Ho, C. S., Chen, H. J., Chiu, N. C., Shen, E. Y. & Lue, H. C. Short-term sulpiride treatment of children and adolescents with tourette syndrome or chronic tic disorder. J. Formos. Med. Assoc. 108, 788–793. https://doi.org/10.1016/s0929-6646(09)60406-x (2009).

    Google Scholar 

  48. Sheehan, D. V. et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J. Clin. Psychiatry 59(Suppl 20), 22–33 (1998).

  49. Sports Medicine Australia, G. A. & Canberra, A. C. T. Sports Medicine Australia Pre-exercise Screening System. (2011).

  50. Algeri, S., Ponzio, F., Dolfini, E. & Jori, A. Biochemical effects of treatment with oral contraceptive steroids on the dopaminergic system of the rat. Neuroendocrinology 22, 343–351. https://doi.org/10.1159/000122643 (1976).

    Google Scholar 

  51. Taylor, C. M. et al. Striatal dopamine synthesis and cognitive flexibility differ between hormonal contraceptive users and nonusers. Cereb. Cortex. 33, 8485–8495. https://doi.org/10.1093/cercor/bhad134 (2023).

    Google Scholar 

  52. Shansky, R. M. & Murphy, A. Z. Considering sex as a biological variable will require a global shift in science culture. Nat. Neurosci. 24, 457–464. https://doi.org/10.1038/s41593-021-00806-8 (2021).

    Google Scholar 

  53. Oldfield, R. C. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97–113. https://doi.org/10.1016/0028-3932(71)90067-4 (1971).

    Google Scholar 

  54. Caley, C. F. & Weber, S. S. Sulpiride: an antipsychotic with selective dopaminergic antagonist properties. Ann. Pharmacother. 29, 152–160. https://doi.org/10.1177/106002809502900210 (1995).

    Google Scholar 

  55. Takano, A. et al. The antipsychotic sultopride is overdosed–a PET study of drug-induced receptor occupancy in comparison with sulpiride. Int. J. Neuropsychopharmacol. 9, 539–545. https://doi.org/10.1017/s1461145705006103 (2006).

    Google Scholar 

  56. Naef, M. et al. Effects of dopamine D2/D3 receptor antagonism on human planning and Spatial working memory. Transl Psychiatry. 7, e1107. https://doi.org/10.1038/tp.2017.56 (2017).

    Google Scholar 

  57. Bond, A. & Lader, M. The use of analogue scales in rating subjective feelings. Br. J. Med. Psychol. 47, 211–218. https://doi.org/10.1111/j.2044-8341.1974.tb02285.x (1974).

    Google Scholar 

  58. Andrews, S. C. et al. Intensity matters: High-intensity interval exercise enhances motor cortex plasticity more than moderate exercise. Cereb. Cortex. 30, 101–112. https://doi.org/10.1093/cercor/bhz075 (2020).

    Google Scholar 

  59. Curtin, D. et al. Ageing attenuates exercise-enhanced motor cortical plasticity. J. Physiol. 601, 5733–5750. https://doi.org/10.1113/JP285243 (2023).

    Google Scholar 

  60. Taylor, E. M. et al. High-intensity acute exercise impacts motor learning in healthy older adults. NPJ Sci. Learn. 9 https://doi.org/10.1038/s41539-024-00220-2 (2024).

  61. Cantarero, G., Tang, B., O’Malley, R., Salas, R. & Celnik, P. Motor learning interference is proportional to occlusion of LTP-like plasticity. J. Neurosci. 33, 4634–4641. https://doi.org/10.1523/JNEUROSCI.4706-12.2013 (2013).

    Google Scholar 

  62. Reis, J. et al. Time- but not sleep-dependent consolidation of tDCS-enhanced visuomotor skills. Cereb. Cortex. 25, 109–117. https://doi.org/10.1093/cercor/bht208 (2015).

    Google Scholar 

  63. McClelland, G. R., Cooper, S. M. & Pilgrim, A. J. A comparison of the central nervous system effects of haloperidol, chlorpromazine and sulpiride in normal volunteers. Br. J. Clin. Pharmacol. 30, 795–803. https://doi.org/10.1111/j.1365-2125.1990.tb05444.x (1990).

    Google Scholar 

  64. Mehta, M. A. et al. Systemic sulpiride modulates striatal blood flow: relationships to Spatial working memory and planning. Neuroimage 20, 1982–1994. https://doi.org/10.1016/j.neuroimage.2003.08.007 (2003).

    Google Scholar 

  65. Freeze, B. S., Kravitz, A. V., Hammack, N., Berke, J. D. & Kreitzer, A. C. Control of basal ganglia output by direct and indirect pathway projection neurons. J. Neurosci. 33, 18531–18539. https://doi.org/10.1523/jneurosci.1278-13.2013 (2013).

    Google Scholar 

  66. Mink, J. W. The basal ganglia and involuntary movements: impaired Inhibition of competing motor patterns. Arch. Neurol. 60, 1365–1368. https://doi.org/10.1001/archneur.60.10.1365 (2003).

    Google Scholar 

  67. Cui, G. et al. Concurrent activation of striatal direct and indirect pathways during action initiation. Nature 494, 238–242. https://doi.org/10.1038/nature11846 (2013).

    Google Scholar 

  68. Nonomura, S. et al. Monitoring and updating of action selection for Goal-Directed behavior through the striatal direct and indirect pathways. Neuron 99, 1302–1314e1305. https://doi.org/10.1016/j.neuron.2018.08.002 (2018).

    Google Scholar 

  69. Augustin, S. M., Loewinger, G. C., O’Neal, T. J., Kravitz, A. V. & Lovinger, D. M. Dopamine D2 receptor signaling on iMSNs is required for initiation and Vigor of learned actions. Neuropsychopharmacology 45, 2087–2097. https://doi.org/10.1038/s41386-020-00799-1 (2020).

    Google Scholar 

  70. Jin, X., Tecuapetla, F. & Costa, R. M. Basal ganglia subcircuits distinctively encode the parsing and concatenation of action sequences. Nat. Neurosci. 17, 423–430 (2014).

    Google Scholar 

  71. Alexander, G. E. & Crutcher, M. D. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci. 13, 266–271. https://doi.org/10.1016/0166-2236(90)90107-l (1990).

    Google Scholar 

  72. Calabresi, P., Picconi, B., Tozzi, A., Ghiglieri, V. & Di Filippo, M. Direct and indirect pathways of basal ganglia: a critical reappraisal. Nat. Neurosci. 17, 1022–1030. https://doi.org/10.1038/nn.3743 (2014).

    Google Scholar 

  73. Mink, J. W. The basal ganglia: focused selection and Inhibition of competing motor programs. Prog Neurobiol. 50, 381–425. https://doi.org/10.1016/s0301-0082(96)00042-1 (1996).

    Google Scholar 

  74. Redgrave, P. et al. Goal-directed and habitual control in the basal ganglia: implications for parkinson’s disease. Nat. Rev. Neurosci. 11, 760–772. https://doi.org/10.1038/nrn2915 (2010).

    Google Scholar 

  75. Prodoehl, J., Corcos, D. M. & Vaillancourt, D. E. Basal ganglia mechanisms underlying precision grip force control. Neurosci. Biobehav Rev. 33, 900–908. https://doi.org/10.1016/j.neubiorev.2009.03.004 (2009).

    Google Scholar 

  76. Wasson, P., Prodoehl, J., Coombes, S. A., Corcos, D. M. & Vaillancourt, D. E. Predicting grip force amplitude involves circuits in the anterior basal ganglia. Neuroimage 49, 3230–3238. https://doi.org/10.1016/j.neuroimage.2009.11.047 (2010).

    Google Scholar 

  77. Grafton, S. T. & Tunik, E. Human basal ganglia and the dynamic control of force during on-line corrections. J. Neurosci. 31, 1600–1605. https://doi.org/10.1523/jneurosci.3301-10.2011 (2011).

    Google Scholar 

  78. Fellows, S. J., Noth, J. & Schwarz, M. Precision grip and parkinson’s disease. Brain 121 (Pt 9), 1771–1784. https://doi.org/10.1093/brain/121.9.1771 (1998).

    Google Scholar 

  79. Roberts, H. C. et al. The association of grip strength with severity and duration of parkinson’s: A Cross-Sectional study. Neurorehabil Neural Repair. 29, 889–896. https://doi.org/10.1177/1545968315570324 (2015).

    Google Scholar 

  80. Brück, A. et al. Striatal subregional 6-[18F]fluoro-L-dopa uptake in early parkinson’s disease: a two-year follow-up study. Mov. Disord. 21, 958–963. https://doi.org/10.1002/mds.20855 (2006).

    Google Scholar 

  81. Ouchi, Y. et al. Microglial activation and dopamine terminal loss in early parkinson’s disease. Ann. Neurol. 57, 168–175. https://doi.org/10.1002/ana.20338 (2005).

    Google Scholar 

  82. Spraker, M. B., Prodoehl, J., Corcos, D. M., Comella, C. L. & Vaillancourt, D. E. Basal ganglia hypoactivity during grip force in drug naïve parkinson’s disease. Hum. Brain Mapp. 31, 1928–1941. https://doi.org/10.1002/hbm.20987 (2010).

    Google Scholar 

  83. Albert, S. T. et al. Competition between parallel sensorimotor learning systems. eLife 11, e65361. https://doi.org/10.7554/eLife.65361 (2022).

    Google Scholar 

  84. Mehta, M. A., Sahakian, B. J., McKenna, P. J. & Robbins, T. W. Systemic sulpiride in young adult volunteers simulates the profile of cognitive deficits in parkinson’s disease. Psychopharmacol. (Berl). 146, 162–174. https://doi.org/10.1007/s002130051102 (1999).

    Google Scholar 

  85. Macedo-Lima, M., Boyd, H. M. & Remage-Healey, L. Dopamine D1 receptor activation drives plasticity in the Songbird auditory pallium. J. Neurosci. 41, 6050–6069. https://doi.org/10.1523/jneurosci.2823-20.2021 (2021).

    Google Scholar 

  86. Walker, M. P., Brakefield, T., Morgan, A., Hobson, J. A. & Stickgold, R. Practice with sleep makes perfect: sleep-Dependent motor skill learning. Neuron 35, 205–211. https://doi.org/10.1016/S0896-6273(02)00746-8 (2002).

    Google Scholar 

  87. Festini, S. B., Preston, S. D., Reuter-Lorenz, P. A. & Seidler, R. D. Emotion and reward are dissociable from error during motor learning. Exp. Brain Res. 234, 1385–1394. https://doi.org/10.1007/s00221-015-4542-z (2016).

    Google Scholar 

  88. Galea, J. M., Mallia, E., Rothwell, J. & Diedrichsen, J. The dissociable effects of punishment and reward on motor learning. Nat. Neurosci. 18, 597–602. https://doi.org/10.1038/nn.3956 (2015).

    Google Scholar 

  89. Schultz, W., Dayan, P. & Montague, P. R. A neural substrate of prediction and reward. Science 275, 1593–1599. https://doi.org/10.1126/science.275.5306.1593 (1997).

    Google Scholar 

  90. Codol, O., Holland, P. J., Manohar, S. G. & Galea, J. M. Reward-Based improvements in motor control are driven by multiple Error-Reducing mechanisms. J. Neurosci. 40, 3604–3620. https://doi.org/10.1523/JNEUROSCI.2646-19.2020 (2020).

    Google Scholar 

  91. Badami, R., Mohammad, V., Gabriele, W., Namazizadeh, M. & and Feedback about more accurate versus less accurate trials. Res. Q. Exerc. Sport. 83, 196–203. https://doi.org/10.1080/02701367.2012.10599850 (2012).

    Google Scholar 

  92. Blain, B. & Sharot, T. Intrinsic reward: potential cognitive and neural mechanisms. Curr. Opin. Behav. Sci. 39, 113–118. https://doi.org/10.1016/j.cobeha.2021.03.008 (2021).

    Google Scholar 

  93. Fitts, P. M. The information capacity of the human motor system in controlling the amplitude of movement. J. Exp. Psychol. 47, 381–391. https://doi.org/10.1037/h0055392 (1954).

    Google Scholar 

  94. Thumser, Z. C., Slifkin, A. B., Beckler, D. T. & Marasco, P. D. Fitts’ law in the control of isometric grip force with naturalistic targets. Front. Psychol. 9, 560. https://doi.org/10.3389/fpsyg.2018.00560 (2018).

    Google Scholar 

  95. Hong, S. & Hikosaka, O. Dopamine-mediated learning and switching in cortico-striatal circuit explain behavioral changes in reinforcement learning. Front. Behav. Neurosci. 5, 15. https://doi.org/10.3389/fnbeh.2011.00015 (2011).

    Google Scholar 

  96. Palminteri, S. et al. Dopamine-dependent reinforcement of motor skill learning: evidence from Gilles de La tourette syndrome. Brain 134, 2287–2301. https://doi.org/10.1093/brain/awr147 (2011).

    Google Scholar 

  97. Wiesel, F. A., Alfredsson, G., Ehrnebo, M. & Sedvall, G. The pharmacokinetics of intravenous and oral sulpiride in healthy human subjects. Eur. J. Clin. Pharmacol. 17, 385–391. https://doi.org/10.1007/bf00558453 (1980).

    Google Scholar 

  98. Snow, N. J. et al. The effect of an acute bout of Moderate-Intensity aerobic exercise on motor learning of a continuous tracking task. PLoS One. 11, e0150039. https://doi.org/10.1371/journal.pone.0150039 (2016).

    Google Scholar 

  99. Statton, M. A., Encarnacion, M., Celnik, P. & Bastian, A. J. A single bout of moderate aerobic exercise improves motor skill acquisition. PLoS One. 10, e0141393. https://doi.org/10.1371/journal.pone.0141393 (2015).

    Google Scholar 

  100. Burstein, E. S. et al. Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist. J. Pharmacol. Exp. Ther. 315, 1278–1287. https://doi.org/10.1124/jpet.105.092155 (2005).

    Google Scholar 

  101. Roth, B. & Driscol, J. P. D. S. P. Ki Database. Psychoactive drug screening program (PDSP). University North. Carolina Chapel Hill United States Natl. Inst. Mental Health (2011).

  102. Gurevich, E. V. & Location, Location, L. The expression of D3 dopamine receptors in the nervous system. Curr. Top. Behav. Neurosci. 60, 29–45. https://doi.org/10.1007/7854_2022_314 (2023).

    Google Scholar 

  103. Eisenegger, C. et al. Role of dopamine D2 receptors in human reinforcement learning. Neuropsychopharmacology 39, 2366–2375. https://doi.org/10.1038/npp.2014.84 (2014).

    Google Scholar 

  104. Mikus, N. et al. Blocking D2/D3 dopamine receptors in male participants increases volatility of beliefs when learning to trust others. Nat. Commun. 14, 4049. https://doi.org/10.1038/s41467-023-39823-5 (2023).

    Google Scholar 

Download references

Acknowledgements

We thank Dr Ziarih Hawi, Daniel Pearce, and Julia Koutoulogenis for their assistance with drug holding and blinding; Claire Cadwallader and Sarah Cohen for their support with data collection; and Bridgitt Shea, Amy Huynh, Huw Jarvis, and Dami Obawede for their assistance with participant recruitment.

Funding

This research was supported by the Australian Research Council Grant, DP200100234, awarded to J.C., and funding awarded to M.B., T.T-J.C, and J.C by the Office of Naval Research (Global). M.B., is supported by the National Health and Medical Research Council. T.T-J.C is supported by the Australian Research Council (DP180102383, FT220100294).

Author information

Author notes

  1. Eleanor M. Taylor and Dylan Curtin contributed equally to this work.

Authors and Affiliations

  1. The Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Melbourne, VIC, 3800, Australia

    Eleanor M. Taylor, Dylan Curtin, Trevor T.-J. Chong, Mark A. Bellgrove & James P. Coxon

  2. Department of Neurology, Alfred Health, Melbourne, VIC, 3004, Australia

    Trevor T.-J. Chong

  3. Department of Clinical Neurosciences, St Vincent’s Hospital, Melbourne, VIC, 3065, Australia

    Trevor T.-J. Chong

Authors
  1. Eleanor M. Taylor
    View author publications

    Search author on:PubMed Google Scholar

  2. Dylan Curtin
    View author publications

    Search author on:PubMed Google Scholar

  3. Trevor T.-J. Chong
    View author publications

    Search author on:PubMed Google Scholar

  4. Mark A. Bellgrove
    View author publications

    Search author on:PubMed Google Scholar

  5. James P. Coxon
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Eleanor M. Taylor: Conceptualization, Methodology, Formal analysis, Investigation, Writing – Original Draft, Visualisation. Dylan Curtin: Conceptualization, Methodology, Formal analysis, Investigation, Writing - Review & Editing. Mark A. Bellgrove: Conceptualization, Methodology, Writing - Review & Editing, Funding acquisition. Trevor T-J. Chong: Conceptualization, Methodology, Writing - Review & Editing, Funding acquisition. James P. Coxon: Conceptualization, Methodology, Formal analysis, Investigation, Writing - Review & Editing, Visualisation, Funding acquisition.

Corresponding author

Correspondence to James P. Coxon.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Taylor, E.M., Curtin, D., Chong, T.TJ. et al. The effect of dopamine D2-like receptor blockade on human motor performance and skill acquisition. Sci Rep (2026). https://doi.org/10.1038/s41598-026-36241-7

Download citation

  • Received: 25 November 2024

  • Accepted: 11 January 2026

  • Published: 20 January 2026

  • DOI: https://doi.org/10.1038/s41598-026-36241-7

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

  • Dopamine
  • D2 receptor
  • Motor sequence learning
  • Skill learning
  • Acute exercise
Download PDF

Advertisement

Explore content

  • Research articles
  • News & Comment
  • Collections
  • Subjects
  • Follow us on Facebook
  • Follow us on Twitter
  • Sign up for alerts
  • RSS feed

About the journal

  • About Scientific Reports
  • Contact
  • Journal policies
  • Guide to referees
  • Calls for Papers
  • Editor's Choice
  • Journal highlights
  • Open Access Fees and Funding

Publish with us

  • For authors
  • Language editing services
  • Open access funding
  • Submit manuscript

Search

Advanced search

Quick links

  • Explore articles by subject
  • Find a job
  • Guide to authors
  • Editorial policies

Scientific Reports (Sci Rep)

ISSN 2045-2322 (online)

nature.com sitemap

About Nature Portfolio

  • About us
  • Press releases
  • Press office
  • Contact us

Discover content

  • Journals A-Z
  • Articles by subject
  • protocols.io
  • Nature Index

Publishing policies

  • Nature portfolio policies
  • Open access

Author & Researcher services

  • Reprints & permissions
  • Research data
  • Language editing
  • Scientific editing
  • Nature Masterclasses
  • Research Solutions

Libraries & institutions

  • Librarian service & tools
  • Librarian portal
  • Open research
  • Recommend to library

Advertising & partnerships

  • Advertising
  • Partnerships & Services
  • Media kits
  • Branded content

Professional development

  • Nature Awards
  • Nature Careers
  • Nature Conferences

Regional websites

  • Nature Africa
  • Nature China
  • Nature India
  • Nature Japan
  • Nature Middle East
  • Privacy Policy
  • Use of cookies
  • Legal notice
  • Accessibility statement
  • Terms & Conditions
  • Your US state privacy rights
Springer Nature

© 2026 Springer Nature Limited

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing