Opioid binding in DYT1 primary torsion dystonia: an 11C-diprenorphine PET study.
The opioid transmitters enkephalin and dynorphin are known to regulate pallidal output and consequently cortical excitability. Indeed, abnormal basal ganglia opioid transmission has been reported in several involuntary movement disorders, including levodopa-induced dyskinesias in Parkinson's disease (PD), tardive dyskinesias/dystonia, Huntington's disease, and Tourette's syndrome. Moreover, a previous 11C-diprenorphine PET study investigating levodopa-induced dyskinesias found reduced opioid receptor availability in PD with but not without dyskinesias. We wished to investigate if a similar alteration in basal ganglia opioid binding was present in DYT1 primary torsion dystonia (PTD). Regional cerebral 11C-diprenorphine binding was investigated in 7 manifesting carriers of the DYT1 gene and 15 age-matched normal controls using a region-of-interest (ROI) approach and statistical parametric mapping (SPM). No difference in regional mean 11C-diprenorphine binding was found between DYT1-PTD and controls, and no correlation between the severity of dystonia and opioid binding was seen. We conclude that aberrant opioid transmission is unlikely to be present in DYT1-PTD and altered opioid transmission is not a common mechanism underlying all disorders of involuntary movement.
Whone
Alan L
AL
Division of Neuroscience and MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom. alan.whone@csc.mrc.ac.uk
Von Spiczak
Sarah
S
Edwards
Mark
M
Valente
Enza-Maria
EM
Hammers
Alexander
A
Bhatia
Kailash P
KP
Brooks
David J
DJ
D000328:Adult; D000368:Aged; D001479:Basal Ganglia / Q000378:metabolism; D001665:Binding Sites; D003342:Corpus Striatum / Q000378:metabolism; D004174:Diprenorphine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004422:Dystonia Musculorum Deformans / Q000235:genetics* / Q000378:metabolism*; D004745:Enkephalins / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D049268:Positron-Emission Tomography; D012720:Severity of Illness Index
D004745:Enkephalins; D018832:Molecular Chaperones; C108175:TOR1A protein, human; D004174:Diprenorphine