title: Similar striatal D2/D3 dopamine receptor availability in adults with Tourette syndrome compared with healthy controls: A [(11) C]-(+)-PHNO and [(11) C]raclopride positron emission tomography imaging study.
abstract: Pharmacological and anatomical evidence implicates striatal dopamine receptors in Tourette syndrome (TS). Nevertheless, results of positron emission tomography (PET) studies of the dopamine system in TS have been inconsistent. We investigated striatal D2/3 dopamine receptors in TS using the radioligands [(11) C]raclopride and [(11) C]-(+)-PHNO, an agonist that binds preferentially to D3 receptors, thus allowing higher sensitivity and measurement of receptors in a high affinity state. Eleven adults with TS and 11 matched healthy control (HC) participants underwent [(11) C]raclopride and [(11) C]-(+)-PHNO PET scans. General linear model was used for voxelwise contrasts of striatal binding potentials (BPND ) between TS and HC participants. Analysis of variance was performed to investigate main effect of radioligand. In addition, BPND values were extracted for ventral, motor, and associative striatum. Finally, we examined the relationship between BPND measures and symptom severity in TS participants. Main effects analyses showed that [(11) C]-(+)-PHNO BPND was higher in ventral striatum, whereas [(11) C]raclopride BPND was higher in motor and associative striatum. There were no significant group differences between TS and HC. Furthermore, TS and HC participants had similar [(11) C]-(+)-PHNO and [(11) C]raclopride BPND in the three striatal subregions. Moreover, there was no significant correlation between BPND and symptom severity. TS and HC participants had similar striatal D2/3 receptor availability measures. These results challenge the assumption that striatal dopamine receptors have a major role in the pathophysiology of TS. Consistent with previous findings, [(11) C]-(+)-PHNO localized preferentially to ventral striatal, D3 receptor-rich regions, in contrast to [(11) C]raclopride, which localized preferentially in the dorsal striatum.
authors: Department of Psychiatry, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors: Elia
authors: E
authors: Abi-Jaoude
authors: Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.|Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain.
authors: Barbara
authors: B
authors: Segura
authors: Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.|Institute of Cognitive Sciences, CNRS, Lyon, France.
authors: Ignacio
authors: I
authors: Obeso
authors: Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.|Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto, Ontario, Canada.
authors: Sang Soo
authors: SS
authors: Cho
authors: Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
authors: Sylvain
authors: S
authors: Houle
authors: Morton and Gloria Shulman Movement Disorder Unit & Edmond J. Safra Program in Parkinson's Disease and the Division of Neurology, Toronto Western Hospital, UHN, University of Toronto, Ontario, Canada.
authors: Anthony E
authors: AE
authors: Lang
authors: Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
authors: Pablo
authors: P
authors: Rusjan
authors: Department of Psychiatry, University Health Network, University of Toronto, Toronto, Ontario, Canada.|Youthdale Treatment Centers, Toronto, Ontario, Canada.
authors: Paul
authors: P
authors: Sandor
authors: Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.|Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto, Ontario, Canada.|Morton and Gloria Shulman Movement Disorder Unit & Edmond J. Safra Program in Parkinson's Disease and the Division of Neurology, Toronto Western Hospital, UHN, University of Toronto, Ontario, Canada.
authors: Antonio P
authors: AP
authors: Strafella
mesh_terms: D000293:Adolescent; D000328:Adult; D003342:Corpus Striatum / Q000378:metabolism*; D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010078:Oxazines; D049268:Positron-Emission Tomography / Q000379:methods*; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D012720:Severity of Illness Index; D005879:Tourette Syndrome / Q000378:metabolism*; D055815:Young Adult
chemical_list: C581293:DRD2 protein, human; C493593:DRD3 protein, human; D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D010078:Oxazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C042631:naxagolide; D020891:Raclopride
keywords: Tourette syndrome; basal ganglia; corpus striatum; dopamine; neostriatum; positron-emission tomography; raclopride; receptors, dopamine; receptors, dopamine D2