DIFFERENTIAL-EFFECTS OF LEVODOPA ON DOPAMINERGIC FUNCTION IN EARLY AND ADVANCED PARKINSONS-DISEASE

The effect of levodopa on L-[C-11]DOPA influx rate was evaluated in pa tients with early and advanced Parkinson's disease (PD) by using posit ron emission tomography (PET). The patients were scanned both drug-fre e and after a subsequent therapeutic levodopa infusion. Regional analy sis of striatal L-[C-11]DOPA influx rate showed a correlation to the d egenerative loss of nerve terminals reported at postmortem analysis in PD. Levodopa induced markedly differential effects on the striatal L- [C-11]DOPA influx rate in early and advanced patients. In patients wit h mild PD, levodopa infusion decreased L-[C-11]DOPA influx, whereas in patients with advanced PD, levodopa induced significant upregulation of L-[C-11]DOPA influx. These changes were confined to the putamen and were, in both patient categories, most prominent in the dorsal part o f the region. The present investigation demonstrates a marked shift in the modulatory action of levodopa with the advancement of PD and sugg ests the induction of positive feedback in advanced PD. These findings could help explain the less graded clinical response to levodopa in a dvanced PD and would thus have importance for the understanding of the pathogenesis underlying motor fluctuations.