Elevated intrasynaptic dopamine release in Tourette's syndrome measured by PET.
OBJECTIVE
Dopaminergic abnormalities in frontal-subcortical circuits have been hypothesized as the underlying pathophysiologic mechanism in Tourette's syndrome. The objective of this study was to test the hypothesis that presynaptic dopamine release from the striatum is abnormal in adults with Tourette's syndrome.


METHODS
Seven adults with Tourette's syndrome and five age-matched comparison subjects each received two positron emission tomography (PET) scans with high specific activity [11C]raclopride. The first scan followed an intravenous injection of saline; the second followed an intravenous injection of amphetamine. The relative dopamine release was estimated as the percentage difference in binding potential between the postsaline and postamphetamine scans.


RESULTS
Binding potential determined after the initial [11C]raclopride scan did not significantly differ between Tourette's syndrome and comparison subjects. After amphetamine challenge, the mean value of intrasynaptic dopamine in the putamen (as determined by true equilibrium bolus estimation) increased by 21% in the subjects with Tourette's syndrome and did not change in the comparison subjects; the mean values increased by 16.9% and decreased by 1.8%, respectively, when measured by the constrained method. Dopamine release in the caudate region was not significantly different in the Tourette's syndrome and comparison subjects.


CONCLUSIONS
Greater putamen dopamine release was seen in adults with Tourette's syndrome than in comparison subjects after a pharmacologic challenge with amphetamine. These results suggest that the underlying pathobiology in Tourette's syndrome is a phasic dysfunction of dopamine transmission.
Singer
Harvey S
HS
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Szymanski
Sally
S
Giuliano
Joseph
J
Yokoi
Fuji
F
Dogan
A Semih
AS
Brasic
James R
JR
Zhou
Yun
Y
Grace
Anthony A
AA
Wong
Dean F
DF
D000328:Adult; D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D018492:Dopamine Antagonists; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D020891:Raclopride; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D013569:Synapses / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D014055:Tomography, Emission-Computed / Q000379:methods / Q000706:statistics & numerical data; D005879:Tourette Syndrome / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology
D018492:Dopamine Antagonists; D020891:Raclopride; D012965:Sodium Chloride; D000661:Amphetamine; D004298:Dopamine