Letter | Published:

Evidence for striatal dopamine release during a video game

Nature volume 393, pages 266268 (21 May 1998) | Download Citation

Subjects

Abstract

Dopaminergic neurotransmission may be involved in learning, reinforcement of behaviour, attention, and sensorimotor integration1,2. Binding of the radioligand 11C-labelled raclopride to dopamine D2 receptors is sensitive to levels of endogenous dopamine, which can be released by pharmacological challenge3,4,5,6,7,8. Here we use 11C-labelled raclopride and positron emission tomography scans to provide evidence that endogenous dopamine is released in the human striatum during a goal-directed motor task, namely a video game. Binding of raclopride to dopamine receptors in the striatum was significantly reduced during the video game compared with baseline levels of binding, consistent with increased release and binding of dopamine to its receptors. The reduction in binding of raclopride in the striatum positively correlated with the performance level during the task and was greatest in the ventral striatum. These results show, to our knowledge for the first time, behavioural conditions under which dopamine is released in humans, and illustrate the ability of positron emission tomography to detect neurotransmitter fluxes in vivo during manipulations of behaviour.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from $8.99

All prices are NET prices.

References

  1. 1.

    , & Responses of monkey dopamine neurons to reward and conditioned stimuli during successive steps of learning a delayed response task. J. Neurosci. 13, 900–913 (1993).

  2. 2.

    & Functions of dopamine in the dorsal and ventral striatum. Semin. Neurosci. 4, 119–127 (1992).

  3. 3.

    et al. Quantitation of carbon-11 labelled raclopride in rat straitum using positron emission tomography. Synapse 12, 47–54 (1992).

  4. 4.

    et al. Microdialysis and SPECT measurements of amphetamine-induced dopamine release in non human primates. Synapse 25, 1–14 (1997).

  5. 5.

    et al. Positron emission tomography analysis of central D1and D2dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Arch. Gen. Psychiatry 49, 538–544 (1992).

  6. 6.

    et al. Imaging endogenous dopamine competition with [11C]raclopride in the human brain. Synapse 16, 255–262 (1994).

  7. 7.

    et al. Effects of central cholinergic blockade on striatal dopamine release measured with positron emission tomography in normal human subjects. Proc. Natl Acad. Sci. USA 90, 11816–11820 (1993).

  8. 8.

    et al. Schizophrenia is associated with elevated amphetamine induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc. Natl Acad. Sci. USA 94, 2569–2574 (1997).

  9. 9.

    , & Responses of monkey dopamine neurons during learning of behavioural reactions. J. Neurophysiol. 67, 145–163 (1992).

  10. 10.

    , , , & Nucleus accumbens dopamine release increases during instrumental level pressing for food but not free food consumption. Pharmacol. Biochem. Behav. 49, 651–660 (1994).

  11. 11.

    & Behaviour-relevant changes in nucleus accumbens dopamine transmission elicited by food reinforcement: an electrochemical study in rat. J. Neurosci. 16, 8160–8169 (1996).

  12. 12.

    , , & In-vivo imaging of neuromodulatory synaptic transmission using PET: a review of relevant neurophysiology. Hum. Brain Mapp. 3, 24–34 (1995).

  13. 13.

    , , , & In vivo imaging of neuromodulation using positron emission tomography: optimal ligand characteristics and task length for detection of activation. Hum. Brain Mapp. 3, 35–55 (1995).

  14. 14.

    , , & The basal ganglia and adaptive motor control. Science 265, 1826–1831 (1994).

  15. 15.

    Dopamine neurons and their role in reward mechanisms. Curr. Opin. Neurobiol. 7, 191–197 (1997).

  16. 16.

    The role of the basal ganglia in motor control: contributions from PET. J. Neurol. Sci. 128, 1–13 (1995).

  17. 17.

    et al. Reproducibility of repeated measures of [11C]raclopride binding in the human brain. J. Nucl. Med. 34, 609–613 (1993).

  18. 18.

    et al. Effects of blood flow on [11C]raclopride binding in the brain: model simulations and kinetic analysis of PET data. J. Cereb. Blood Flow Metab. 14, 995–1010 (1994).

  19. 19.

    et al. Kinetic modelling of [11C]raclopride: combined PET-microdialysis studies. J. Cereb. Blood Flow Metab. 9, 932–942 (1997).

  20. 20.

    , , & The relationship between learning-performance and dopamine in the prefrontal cortex of the rat. Neurosci. Lett. 177, 83–86 (1993).

  21. 21.

    et al. Statistical parametric maps in functional imaging: a general linear approach. Hum. Brain Mapp. 2, 189–210 (1995).

  22. 22.

    , , & Selective activation of the mesocortical dopaminergic system by stress. Nature 263, 242–244 (1976).

  23. 23.

    The dopamine synapse and the notion of “pleasure centres” in the brain. Trends Neurosci. 3, 91–94 (1980).

  24. 24.

    , , & Parametric imaging of ligand-receptor binding in PET using a simplified reference region model. Neuroimage 6, 279–287 (1997).

  25. 25.

    & Simplified reference tissue model for PET receptor studies. Neuroimage 4, 153–158 (1996).

  26. 26.

    , , , & in Quantification of Brain Function Using PET (eds Myers, R., Cunningham, V., Bailey, D. & Jones, T.) 301–306 (Academic, London, (1996)).

Download references

Acknowledgements

M.J.K. was supported by a grant from the Theodore and Vada Stanley Foundation Research Program; R.N.G., V.J.C., D.J.B. and P.M.G. were supported by the Medical Research Council; and A.D.L. was supported by a fellowship from the British Brain and Spine Foundation. We thank P. Dayan and L. Farde for discussions and comments on the manuscript; and K. Friston, A. Holmes and J.Ashburner for statistical advice and help with the SPM analysis.

Author information

Affiliations

  1. MRC Cyclotron Unit, Hammersmith Hospital, DuCane Road, London W12 0NN, UK, and Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, St Dunstan's Road, London W6 8RP, UK

    • M. J. Koepp
    • , R. N. Gunn
    • , A. D. Lawrence
    • , V. J. Cunningham
    • , A. Dagher
    • , T. Jones
    • , D. J. Brooks
    • , C. J. Bench
    •  & P. M. Grasby

Authors

  1. Search for M. J. Koepp in:

  2. Search for R. N. Gunn in:

  3. Search for A. D. Lawrence in:

  4. Search for V. J. Cunningham in:

  5. Search for A. Dagher in:

  6. Search for T. Jones in:

  7. Search for D. J. Brooks in:

  8. Search for C. J. Bench in:

  9. Search for P. M. Grasby in:

Corresponding author

Correspondence to P. M. Grasby.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/30498

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.