PET- and MRI-based assessment of glucose utilization, dopamine receptor binding, and hemodynamic changes after lesions to the caudate-putamen in primates.
In vivo physiological changes associated with striatal pathology were determined by measurement of glucose utilization, binding to D1 receptors and dopamine reuptake sites, regional blood flow, and behavior before and after unilateral quinolinate infusions into caudate-putamen in three nonhuman primates (Macaca fascicularis and Macaca mulatta). Following the quinolinate lesion, symptoms similar to those of Huntington's disease could be induced by dopamine agonist treatment. In addition, all animals showed a long-term decrease in glucose utilization in the caudate by [19F]fluoro-2-deoxy-D-glucose positron emission tomography (PET). At 4-6 weeks following the lesion the average decrease in glucose utilization in the caudate-putamen was between 40 and 50% of the prelesion values in primates with large lesions. Corresponding caudate-putamen regional blood volume in these animals showed a 61 and 74% decrease as studied by magnetic resonance imaging with somewhat smaller changes observed in an index of cerebral blood flow. The caudate-putamen uptake rate constants for D1 receptors reflected neuronal loss and decreased by an average 40 and 48%, as determined by 11C-labeled Schering compound (SCH 39 166) and PET. Dopamine reuptake sites and fibers assessed by the 11C-labeled cocaine analog, WIN 35 428 compound, and PET showed a temporary decrease in areas with mild neuronal loss and a long-term decrease in striatal regions with severe destruction. These results, which were consistent with behavioral changes and neuropathology seen at postmortem examination, can be related to in vivo physiological studies of Huntington's disease patients.
Brownell
A L
AL
Department of Radiology, Massachusetts General Hospital, Boston 02114.
Hantraye
P
P
Wullner
U
U
Hamberg
L
L
Shoup
T
T
Elmaleh
D R
DR
Frim
D M
DM
Madras
B K
BK
Brownell
G L
GL
Rosen
B R
BR
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002421:Caudate Nucleus / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006439:Hemodynamics; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D009069:Movement Disorders / Q000209:etiology; D009411:Nerve Endings / Q000378:metabolism; D011699:Putamen / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D017378:Quinolinic Acid / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000378:metabolism*; D014055:Tomography, Emission-Computed; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D011954:Receptors, Dopamine; D014446:Tyrosine 3-Monooxygenase; D000110:Acetylcholinesterase; D017378:Quinolinic Acid; D005947:Glucose; D001058:Apomorphine; D004298:Dopamine