Get access

Endogenous dopamine release after pharmacological challenges in Parkinson's disease

Authors

  • Paola Piccini MD,

    Corresponding author
    1. MRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom
    • MRC Cyclotron Building, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road W12 0NN, London United Kingdom
    Search for more papers by this author
  • Nicola Pavese MD,

    1. MRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom
    Search for more papers by this author
  • David J. Brooks MD, DSc, FRCP

    1. MRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom
    2. Institute of Neurology, London, United Kingdom
    Search for more papers by this author

Abstract

Using 11C-raclopride positron emission tomography after methamphetamine challenge, we have evaluated regional brain changes in synaptic dopamine (DA) levels in six volunteers and six advanced Parkinson's disease (PD) patients. The pharmacological challenge induced significant release of endogenous DA in putamen not only in the normal subjects, as reflected by a 25.2% reduction in 11C-raclopride binding potential as compared with placebo, but also in the PD patients (6.8%). In individual PD patients, we found a correlation between putamen DA release and DA storage, as measured by 18F-dopa uptake. Localization of significant changes in 11C-raclopride binding after methamphetamine at a voxel level with statistical parametric mapping identified striatal and prefrontal DA release in both cohorts. Statistical comparisons between normal subjects and PD confirmed significantly reduced DA release in striatal areas in PD, but normal levels of prefrontal DA release. In conclusion, significant endogenous DA release can still be induced by pharmacological challenges in the putamen of advanced PD patients, and this release correlates with residual DA storage capacity. Our data also show that the capacity to release normal DA levels in prefrontal areas after a pharmacological challenge is preserved in severe stages of the disease. Ann Neurol 2003

Ancillary