Chronic Exposure to Dopamine Agonists Affects the Integrity of Striatal D Receptors in Parkinson's Patients

We aimed to investigate the integrity and clinical relevance of striatal dopamine receptor type-2 (DR) availability in Parkinson's disease (PD) patients. We studied 68 PD patients, spanning from early to advanced disease stages, and 12 healthy controls. All participants received one [C]raclopride PET scan in an OFF medication condition for quantification of striatal DR availability . Parametric images of [C]raclopride non-displaceable binding potential were generated from the dynamic [C]raclopride scans using implementation of the simplified reference tissue model with cerebellum as the reference tissue. PET data were interrogated for correlations with clinical data related to disease burden and dopaminergic treatment. PD patients showed a mean 16.7% decrease in caudate DR and a mean 3.5% increase in putaminal DR availability compared to healthy controls. Lower caudate [C]raclopride BP correlated with longer PD duration. PD patients on dopamine agonist treatment had 9.2% reduced DR availability in the caudate and 12.8% in the putamen compared to PD patients who never received treatment with dopamine agonists. Higher amounts of lifetime dopamine agonist therapy correlated with reduced DRs availability in both caudate and putamen. No associations between striatal DR availability and levodopa treatment and dyskinesias were found. In advancing PD the caudate and putamen DR availability are differentially affected. Chronic exposure to treatment with dopamine agonists, but no levodopa, suppresses striatal DR availability, which may have relevance to output signaling to frontal lobes and the occurrence of executive deficits, but not dyskinesias.