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.
Nilsson J, et al. Synthesis and evaluation of pharmacological and pharmacokinetic properties of monopropyl analogs of 5-, Figure. Choreatic events at baseline and following 0.5 mg/kg (-)-OSU6162 in a patient with Huntington's disease. Chorea was assessed from standardized video recordings made with the patient instructed to sit still in a chair. Each bar represents the mean number of choreatic events counted from the videotape recordings during three 10-minute sessions. Baseline value comprises ratings from 2 consecutive days.
Parkinson's disease (PD) is characterized by an uneven and progressive loss of nigrostriatal dopaminergic neurons. It is hypothesized that the physiological basis for the therapeutic response in early stages of PD is the ability for the partially and unevenly denervated dopaminergic system to restore and normalize dopaminergic influence in functionally segregated subregions of the basal ganglia. To investigate this hypothesis, patients with early and uncomplicated PD were investigated with positron emission tomography by using a two-tracer protocol yielding a measure of dopamine transporter-corrected dopamine synthesis capacity. Compared with controls, patients with PD exhibited a considerable increase in dopamine transporter-corrected dopamine synthesis capacity. The increase showed an inverse dependence on the structural integrity in as much as the highest rate was measured in the most denervated region, the dorsal part of putamen (198% of control value). A therapeutic challenge with antiparkinsonian medication state-dependently decreased dopaminergic activity. Thus, it is demonstrated that dopaminergic degeneration in PD is accompanied by a conspicuous acceleration of presynaptic dopaminergic activity, which is state-dependently down-regulated by dopaminomimetic treatment. It is suggested that homeostatic mechanisms acting to maintain congruity within the dopaminergic system are functionally intact in early PD.
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