BACKGROUND: Several lines of evidence suggest that dopamine (DA)-influenced neuronal pathways may malfunction in Tourette Syndrome (TS). A dopamine-responsive abnormality of brain function in TS could be either presynaptic or postsynaptic. Some PET studies support the hypothesis of presynaptic abnormalities in levodopa uptake, dopamine synthesis, or dopamine release. Alternatively, presynaptic dopaminergic function could be normal in TS but dopamine-sensitive abnormalities could exist in striatum, pallidum, thalamus, or cortex. METHODS: In this study we directly tested the presynaptic hypothesis using a new approach. We used positron emission tomography (PET) and [11C]raclopride (RAC*) to measure synaptic dopamine release in response to levodopa and placebo infusions (with carbidopa) in 5 neuroleptic-naïve adults with TS and 5 matched control subjects. The primary analysis examined RAC* binding potential (BPND) in predefined volumes of interest (VOIs). A secondary analysis compared BPND voxel by voxel over the entire brain. RESULTS: (1) Overall, baseline RAC* BPND did not differ significantly between groups, though nucleus accumbens BPND was higher in TS (16%, p=0.051). (2) Across regions, DA release declined from before to during infusion (p=0.014), including with placebo. (3) This decline was smaller in TS (p=0.080). (4) Levodopa’s effect on BPND differed significantly in right midbrain (p=0.002, corrected), where levodopa displaced RAC* by 59% in control subjects but increased BPND 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 has implications for other RAC* PET studies. The smaller magnitude of the decrease 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 was not predicted, but may signify an abnormal response to dopaminergic stimulation in TS. These findings invite confirmation in a larger sample.
Levodopa-stimulated dopamine release in Tourette syndrome(2013)
Publication DateJune 6, 2013