Alterations in opioid receptor binding in Parkinson's disease patients with levodopa-induced dyskinesias.
Levodopa-induced dyskinesias remain a major challenge in the therapeutic management of Parkinson's disease (PD). Their etiology is unknown although dysfunction of striatal opioid transmission has been implicated in experimental models of PD. To determine whether the opioid system is involved in human dyskinetic PD, we measured in vivo opioid receptor binding in PD patients with and without levodopa-induced dyskinesias, using positron emission tomography (PET) and the opioid receptor ligand [11C]diprenorphine. Striatal and thalamic/occipital uptake ratios were calculated using a region of interest (ROI) approach. In addition, we used statistical parametric mapping (SPM) and images reflecting the volume of distribution of [11C]diprenorphine to assess changes in cerebral receptor binding on a voxel-by-voxel basis. By using the ROI approach, we found significantly reduced striatal and thalamic opioid binding in dyskinetic, but not in nondyskinetic, PD patients. The SPM approach confirmed reduced availability in these areas and, in addition, showed decreased cingulate and increased prefrontal opioid receptor binding in the dyskinetic patients. Our findings confirm that altered opioid transmission is part of the pathophysiology of levodopa-induced dyskinesias in PD and support further investigation into the role of opioid agents in the management of these involuntary movements.
Piccini
P
P
MRC Cyclotron Unit, Hammersmith Hospital, London, UK.
Weeks
R A
RA
Brooks
D J
DJ
D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D002421:Caudate Nucleus / Q000737:chemistry; D004174:Diprenorphine; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009292:Narcotic Antagonists; D009778:Occipital Lobe / Q000737:chemistry; D010300:Parkinson Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D011699:Putamen / Q000737:chemistry; D011957:Receptors, Opioid / Q000378:metabolism*; D013787:Thalamic Nuclei / Q000737:chemistry
D000978:Antiparkinson Agents; D002250:Carbon Radioisotopes; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D004174:Diprenorphine; D007980:Levodopa