Levodopa-stimulated dopamine release in Tourette syndrome
- Published
- Accepted
- Subject Areas
- Neuroscience, Neurology, Psychiatry and Psychology, Radiology and Medical Imaging
- Keywords
- dopamine D2 receptor, raclopride, positron emission tomography, PET, levodopa, dopamine, Tourette syndrome, nucleus accumbens, substantia nigra, midbrain
- Copyright
- © 2014 Black et al.
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Cite this article
- 2014. Levodopa-stimulated dopamine release in Tourette syndrome. PeerJ PrePrints 2:e30v2 https://doi.org/10.7287/peerj.preprints.30v2
Abstract
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 [11C]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 (BPND) in predefined volumes of interest (VOIs). A secondary analysis compared BPND voxel by voxel over the entire brain.
RESULTS: (1) Baseline RAC* BPND did not differ significantly between groups, though nucleus accumbens BPND 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 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 may have implications for other RAC* PET studies. The smaller decrease of BPND 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.
Author Comment
This version was submitted for peer review. It includes several small changes to the text, a couple of added references, and cleaner figures.