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Dopamine autoreceptor function is lost in advanced Parkinson’s disease

From the Department of Neurology (Drs. Ekesbo and Tedroff), University Hospital, Uppsala; Karolinska Institute (Drs. Rydin and Sydow), Danderyd Hospital, Division of Neurology, Danderyd; Uppsala University PET Centre (R. Torstenson and Dr. Låengström), Uppsala University, Uppsala, Sweden.

Address correspondence and reprint requests to Dr. Joakim Tedroff, Department of Neurology, University Hospital, S-75185 Uppsala, Sweden.

OBJECTIVE: Regional presynaptic dopaminergic function and its regulation by dopamine agonists in different stages of PD can be measured by L-[¹¹C]dopa and PET. In the current investigation, we studied the effects of therapeutic apomorphine on L-[¹¹C]dopa uptake in patients with early and advanced PD.

BACKGROUND: With disease progression and chronic dopamine agonist treatment, motor response complications supervene in a majority of PD patients. It is assumed that both presynaptic and postsynaptic changes in the dopaminergic system act to modify dopaminergic efficacy.

METHODS: Patients with early and advanced stages of PD were included in the study. All patients were investigated twice with PET and L-[¹¹C]dopa drug free and during a subsequent standardized therapeutic apomorphine infusion.

RESULTS: Subregional analysis of the striatum showed differences in the effects of apomorphine infusion on the L-[¹¹C]dopa influx rate in the two patient categories. In patients with early and uncomplicated PD, apomorphine infusion decreased the L-[¹¹C]dopa influx rate. This decrease was most pronounced in the dorsal part of the putamen. In advanced PD patients, apomorphine did not affect the striatal L-[¹¹C]dopa influx rate.

CONCLUSIONS: We suggest that in mild and stable PD an upregulated presynaptic inhibitory feedback regulation, particularly in the dorsal putamen, acts to maintain congruity within the dopaminergic system in response to antiparkinsonian medication. However, this inhibitory feedback regulation is diminished with the progression of nigrostriatal degeneration and chronic dopamine agonist treatment.

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