Abnormal dopamine uptake sites in postmortem striatum from patients with Tourette's syndrome.
The dopamine hypothesis for Tourette's syndrome proposes that the disorder is pathologically related either to an excessive amount of dopamine or to supersensitive receptors. To evaluate these proposals, pre- and postsynaptic markers of dopamine metabolism were measured in postmortem striatum from three adults with the diagnosis of Tourette's syndrome. Neuronal dopamine uptake carrier sites [( 3H]mazindol binding) were significantly increased in number over control values by 37% in the caudate and by 50% in the putamen. High-pressure liquid chromatographic assays of dopamine and its primary metabolites, homovanillic acid and 3,4-dihydroxyphenylacetic acid, showed normal findings. D1 and D2 subtypes of dopaminergic receptors [( 3H]SCH 23390 and [3H]spiperone binding, respectively) showed only slight alterations, presumably due to treatment with neuroleptics. The concentration of adenosine 3',5'-monophosphate (cyclic AMP) in putamen was reduced by 23%. Our data support earlier proposals of a dopaminergic abnormality in TS, but suggest that the mechanism involves a significant alteration of uptake sites. We speculate that increases in carrier site binding indicate an enhanced dopamine innervation within the striatum.
Singer
H S
HS
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.
Hahn
I H
IH
Moran
T H
TH
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000328:Adult; D002421:Caudate Nucleus / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006719:Homovanillic Acid / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011699:Putamen / Q000378:metabolism; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000378:metabolism; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D005879:Tourette Syndrome / Q000378:metabolism*
D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid