Functional mapping of dopaminergic transmission]

Patients with Parkinson's disease (PD) are impaired when performing cognitive tasks such as mental operations and working memory paradigms, which engage frontal lobe regions. These impairments may reflect degeneration of either nigrostriatal or mesocortical dopaminergic projections. D2 receptor antagonist 11C-raclopride (RAC) with positron emission tomography (PET) now provides an in vivo approach for investigating dopaminergic transmission by monitoring changes in synaptic dopamine levels during task performance, Our RAC PET study suggests that the capacity to release dopamine during a working memory task is impaired in the striatum but relatively preserved in the medial prefrontal cortex in patients with PD. This pattern of dopamine release is in accordance with our previous H2(15)O PET findings showing hypoactivity of the striatum during a mental operation task in PD. These PET findings support a view that degeneration of nigrostriatal dopaminergic projection causing disruption of the cortico-basal ganglia circuit contributes to the cognitive impairments observed in PD. The findings also implicates that mesocortical dopaminergic function may be preserved in PD. Since excessive stimulation of dopamine receptors in the frontal cortex can rather deteriorate its function, the benefit in the striatum and the risk in the frontal cortex should be properly evaluated for dopamine replacement therapy.