title: Abnormal dopamine uptake sites in postmortem striatum from patients with Tourette's syndrome.
abstract: 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.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: H S
authors.initials: HS
authors.lastname: Singer
authors.forename: I H
authors.initials: IH
authors.lastname: Hahn
authors.forename: T H
authors.initials: TH
authors.lastname: Moran
mesh_terms: 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*
chemical_list: D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid