Influence of L-dopa and pramipexole on striatal dopamine transporter in early PD

Background: Animal data indicate that chronic exposure to dopaminergic drug s can alter levels of the dopamine transporter (DAT), which is critically i nvolved in regulation of synaptic dopamine levels. DAT changes could influe nce the response to therapy in PD. Methods: A randomized, assessor-blinded, placebo-controlled clinical trial was performed in subjects with early PD to determine whether L-dopa or pramipexole might regulate striatal DAT bind ing as measured by PET with [C-11]RTI-32. Thirty clinically asymmetrical pa tients were randomly assigned to receive 6 weeks of L-dopa (300/75 mg/d), p ramipexole (1.5 mg/d), or placebo; PET studies were performed before and af ter treatment. Results: Mean interval change in DAT binding was significant ly reduced by 16% to 22% in all striatal regions (caudate, anterior and pos terior putamen) of the L-dopa-treated patients, whereas significant changes in the pramipexole-treated patients were limited to the contralateral caud ate (-15%), ipsilateral anterior putamen (-14%), and posterior putamen (-20 %). In the placebo group there were significant changes in contralateral ca udate (-11%) and ipsilateral anterior putamen (-12%). L-dopa and pramipexol e produced similar clinical benefit. Conclusions: Short-term therapy with L -dopa and, to a lesser extent, pramipexole can modestly down-regulate stria tal DAT in patients with early PD. Decreased striatal DAT could increase do paminergic neurotransmission with potential benefit, but might also play a role in the development of dopamine-related response fluctuations in patien ts with advanced disease. Our data also suggest caution in interpretation o f longitudinal imaging studies employing DAT to assess disease progression and the efficacy of neuroprotective agents.