Dopamine autoreceptor function is lost in advanced Parkinson's disease

Objective: Regional presynaptic dopaminergic function and its regulation by dopamine agonists in different stages of PD can be measured by L-[C-11]dop a and PET. In the current investigation, we studied the effects of therapeu tic apomorphine on L-[C-11]dopa uptake in patients with early and advanced PD. Background: With disease progression and chronic dopamine agonist treat ment, motor response complications supervene in a majority of PD patients. It is assumed that both presynaptic and postsynaptic changes in the dopamin ergic system act to modify dopaminergic efficacy. Methods: Patients with ea rly and advanced stages of PD were included in the study. All patients were investigated twice with PET and L-[C-11]dopa drug free and during a subseq uent standardized therapeutic apomorphine infusion. Results: Subregional an alysis of the striatum showed differences in the effects of apomorphine inf usion on the L-[C-11]dopa influx rate in the two patient categories. In pat ients with early and uncomplicated PD, apomorphine infusion decreased the L -[C-11]dopa influx rate. This decrease was most pronounced in the dorsal pa rt of the putamen. In advanced PD patients, apomorphine did not affect the striatal L-[C-11]dopa influx rate. Conclusions: We suggest that in mild and stable PD an upregulated presynaptic inhibitory feedback regulation, parti cularly in the dorsal putamen, acts to maintain congruity within the dopami nergic system in response to antiparkinsonian medication. However, this inh ibitory feedback regulation is diminished with the progression of nigrostri atal degeneration and chronic dopamine agonist treatment.