Long-term changes of striatal dopamine D-2 receptors in patients with Parkinson's disease: A study with positron emission tomography and [C-11]Raclopride

We used [C-11]raclopride (RACLO) and positron emission tomography (PET) to study longitudinally striatal dopamine D-2 receptor binding in nine patients with Parkinson's disease (PD) at an early drug-naive stage and 3-5 years later, when motor fluctuations had appeared in seven of them. Patients were treated with a combination of levodopa and dopamine agonists. Data were compared with 10 healthy controls in the same age range. Initially, patients with PD showed a significant increase of RACLO uptake in the putamen compared with controls (p < 0.04). The caudate nucleus revealed values in the normal range. Alter 3-5 years, RACLO binding was significantly reduced in the putamen (p < 0.03) and caudate nucleus (p < 0.03) compared with baseline. Values were now in the control range in the putamen and reduced in the caudate nucleus (p < 0.05). The clinical score at ''off'' had significantly worsened (p < 0.0005) compared with the first PET scan. The nine PD patients reported here had already been investigated 3-4 months after therapy began and at that time did not show a reduction of the initially increased RACLO binding capacity (data published previously). These results indicate long-term downregulation of striatal dopamine D-2 receptor binding in PD. Receptor changes in the striatum of patients with PD may be induced by chronic dopaminergic therapy or occur independently of treatment, as a result of structural adaptation of the postsynaptic dopaminergic system to the progressive decline of nigrostriatal neurons.