Striatal D2 receptors in symptomatic and asymptomatic carriers of dopa-responsive dystonia measured with [11C]-raclopride and positron-emission tomography.
We tested the hypothesis that asymptomatic carriers of dopa-responsive dystonia (DRD) have increased dopamine D2 receptors in the striatum that protect them from the clinical manifestations of dopaminergic deficiency. We examined striatal D2-receptor binding in (1) symptomatic subjects (treated and untreated) and (2) asymptomatic gene carriers. Using [11C]-raclopride PET, we found elevated striatal D2-receptor binding in both groups. In one of our drug-naive symptomatic subjects, 7 months of treatment with levodopa/carbidopa did not affect the receptor binding as measured on a second scan. We conclude that increased D2-receptor binding in DRD may be a homeostatic response to the dopaminergic deficit in subjects carrying the DRD gene, but is not the sole factor determining the clinical state of these individuals.
Kishore
A
A
Neurodegenerative Disorders Centre, Vancouver Hospital and Health Sciences Centre, British Columbia, Canada.
Nygaard
T G
TG
de la Fuente-Fernandez
R
R
Naini
A B
AB
Schulzer
M
M
Mak
E
E
Ruth
T J
TJ
Calne
D B
DB
Snow
B J
BJ
Stoessl
A J
AJ
D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D001708:Biopterins / Q000134:cerebrospinal fluid; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000737:chemistry*; D015259:Dopamine Agents / Q000008:administration & dosage; D018492:Dopamine Antagonists; D004421:Dystonia / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006579:Heterozygote; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012457:Salicylamides; D012737:Sex Factors; D013570:Synaptic Membranes / Q000737:chemistry; D014055:Tomography, Emission-Computed / Q000379:methods*
D002250:Carbon Radioisotopes; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D001708:Biopterins; D020891:Raclopride; D007980:Levodopa