Levodopa-stimulated dopamine release in Tourette syndrome

RATIONALE: Several lines of evidence suggest that dopamine (DA)-influenced neuronal pathways may malfunction in Tourette Syndrome (TS). Some PET studies support the hypothesis of presynaptic abnormalities in levodopa uptake, dopamine synthesis, or dopamine release. OBJECTIVE: Directly test the presynaptic hypothesis using a new approach. METHODS: We used positron emission tomography (PET) and [ 11 C]raclopride (RAC*) to measure synaptic dopamine release before and during levodopa and placebo infusions (with carbidopa) in 5neuroleptic-naïve adults with TS and 5 matched control subjects. The primary analysis examined RAC* binding potential (BP ND ) in predefined volumes of interest (VOIs). A secondary analysis compared BP ND voxel by voxel over the entire brain. RESULTS: (1) Baseline RAC* BP ND did not differ significantly between groups, though nucleus accumbens BP ND was higher in TS (16%, p=0.051). (2) DA release declined from before to during infusions (p=0.014), including with placebo. (3) This decline was smaller in TS (p=0.080). (4) Levodopa’s effect on BP ND differed significantly in right midbrain (p=0.002, corrected), where levodopa displaced RAC* by 59% in control subjects but increased BP ND by 74% in TS subjects, and in parahippocampal gyrus (p=0.02, corrected). DISCUSSION: Our finding that a before/after RAC* design is confounded by time and/or expectation effects may have implications for other RAC* PET studies. The smaller decrease of BP ND with time in TS may be attributable to impaired habituation to the scan environment. Levodopa’s opposite effect on RAC* binding in TS dopaminergic midbrain but may signify an abnormal response to dopaminergic stimulation in TS.