Objective: To investigate whether dopamine D2 and D3 receptor subtypes (D2/3Rs) outside the caudate-putamen are affected in PD.
Background: Alterations in striatal D2-like dopamine receptors in PD have been extensively demonstrated using PET, but there are no studies focusing on extrastriatal D2/3Rs.
Methods: Fourteen unmedicated patients with idiopathic early PD with predominantly left-sided symptoms, 14 levodopa-medicated patients with advanced PD, and 20 normal age-matched controls were examined using PET. PET scanning was performed with a novel high-affinity D2/3R radioligand ([11C]FLB 457) and a PET scanner in three-dimensional mode.
Results: In advanced PD, the binding potential of [11C]FLB 457 in the dorsolateral prefrontal cortex was decreased by 40% (p < 0.01), in the anterior cingulate cortex by 20% (p < 0.01), and in the medial thalamus by 17% (p < 0.05) compared with healthy controls. In early PD, the extrastriatal [11C]FLB 457 binding potentials were not significantly different compared with the control group. However, the binding potential in the anterior cingulate cortex (29%; p < 0. 05) was higher in early PD compared with advanced PD.
Conclusions: These results imply that the D2/3 receptor subtypes outside the striatum are affected in advanced PD but not in the early stages of the disease, and that this receptor decline is present in the anterior cingulate cortex, the dorsolateral prefrontal cortex, and the thalamus.
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http://dx.doi.org/10.1212/wnl.54.7.1482 | DOI Listing |
J Neurosci Res
April 2021
Brain Health Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, ON, Canada.
Rapid eye movement sleep behavior disorder (RBD) is a common condition found in more than 50% of the patients with Parkinson's disease (PD). Molecular imaging shows that PD with RBD (PD-RBD+) have lower striatal dopamine transporter activity within the caudate and putamen relative to PD without RBD (PD-RBD-). However, the characterization of the extra-striatal dopamine within the mesocortical and mesolimbic pathways remains unknown.
View Article and Find Full Text PDFJ Neurosci Res
March 2021
Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada.
Cognitive decline in Parkinson's disease (PD) is a common sequela of the disorder that has a large impact on patient well-being. Its physiological etiology, however, remains elusive. Our study used graph theory analysis to investigate the large-scale topological patterns of the extrastriatal dopamine D2 receptor network.
View Article and Find Full Text PDFIntroduction: Stress is one of the greatest burdens of our society and often implies impairments in cognitive and emotional functions. Here, we hypothesise that changes in the brain's dopamine (DA)-based mesocorticolimbic projec-tions in patients with work-related stress (adjustment disorder) will manifest themselves as altered glucose metabolism in relation to neural activity, and as altered DA radiotracer binding potentials at the relevant receptors.
Methods: Subjects and healthy controls undergo neuropsychiatric tests and PET/MRI with three tracers: 18F-fluorodeoxyglucose to measure glucose metabolism as a marker of neural activity, 11C-raclopride to explore binding potentials in the striatum, and 11C-FLB 457 to study possibly impaired mesocortical dopaminergic transmission in the cortex.
Schizophr Bull
April 2019
Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Evidence from several lines of research suggests decreased dopamine release in the prefrontal cortex as the neurochemical correlates of cognitive deficits in schizophrenia (SCZ). However, in vivo examination of cortical hypodopaminergia using positron emission tomography (PET) during cognitive task performance in SCZ remains to be investigated. We examined dopamine release in anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC), using PET while participants were performing a cognitive task.
View Article and Find Full Text PDFSynapse
September 2018
Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Studies in nonhuman primates and humans have demonstrated that amphetamine-induced dopamine release in the cortex can be measured with [ C]FLB 457 and PET imaging. This technique has been successfully used in recent clinical studies to show decreased dopamine transmission in the prefrontal cortex in schizophrenia and alcohol dependence. Here, we present data from a cohort of twelve healthy controls in whom an oral amphetamine challenge (0.
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