Endogenous dopamine release after pharmacological challenges in Parkinson's disease

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