PET IMAGING OF THE BRAIN OPIOID SYSTEM: FOCUS ON ALCOHOL DEPENDENCE.

2004 ◽  
Vol 28 (Supplement) ◽  
pp. 72A
Author(s):  
James Frost
Keyword(s):  
Alcohol Dependence ◽  
Pet Imaging ◽  
Opioid System ◽  
The Brain ◽  
System Focus

scholarly journals Potential for imaging the high-affinity state of the 5-HT1B receptor: a comparison of three PET radioligands with differing intrinsic activity

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anton Lindberg ◽  
Ryosuke Arakawa ◽  
Tsuyoshi Nogami ◽  
Sangram Nag ◽  
Magnus Schou ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Specific Binding ◽  
Occipital Cortex ◽  
Intrinsic Activity ◽  
High Affinity ◽  
G Protein Coupled ◽  
Dose Dependent ◽  
The Brain ◽  
Agonist Affinity States ◽  
Different Doses

Abstract Background Over the last decade, a few radioligands have been developed for PET imaging of brain 5-HT1B receptors. The 5-HT1B receptor is a G-protein-coupled receptor (GPCR) that exists in two different agonist affinity states. An agonist ligand is expected to be more sensitive towards competition from another agonist, such as endogenous 5-HT, than an antagonist ligand. It is of interest to know whether the intrinsic activity of a PET radioligand for the 5-HT1B receptor impacts on its ability to detect changes in endogenous synaptic 5-HT density. Three high-affinity 11C-labeled 5-HT1B PET radioligands with differing intrinsic activity were applied to PET measurements in cynomolgus monkey to evaluate their sensitivity to be displaced within the brain by endogenous 5-HT. For these experiments, fenfluramine was pre-administered at two different doses (1.0 and 5.0 mg/kg, i.v.) to induce synaptic 5-HT release. Results A dose-dependent response to fenfluramine was detected for all three radioligands. At the highest dose of fenfluramine (5.0 mg/kg, i.v.), reductions in specific binding in the occipital cortex increased with radioligand agonist efficacy, reaching 61% for [11C]3. The most antagonistic radioligand showed the lowest reduction in specific binding. Conclusions Three 5-HT1B PET radioligands were identified with differing intrinsic activity that could be used in imaging high- and low-affinity states of 5-HT1B receptors using PET. From this limited study, radioligand sensitivity to endogenous 5-HT appears to depend on agonist efficacy. More extensive studies are required to substantiate this suggestion.

scholarly journals Association of the OPRM1 A118G polymorphism and Pavlovian-to-instrumental transfer: Clinical relevance for alcohol dependence

2021 ◽  
pp. 026988112199199 ◽  
Author(s):  
Miriam Sebold ◽  
Maria Garbusow ◽  
Deniz Cerci ◽  
Ke Chen ◽  
Christian Sommer ◽  
...  
Keyword(s):  
Alcohol Dependence ◽  
Opioid Receptor ◽  
Mechanistic Model ◽  
Critical Role ◽  
Opioid System ◽  
Operant Behaviour ◽  
Oprm1 Gene ◽  
Potential Biomarker ◽  
A118g Polymorphism

Background: Pavlovian-to-instrumental transfer (PIT) quantifies the extent to which a stimulus that has been associated with reward or punishment alters operant behaviour. In alcohol dependence (AD), the PIT effect serves as a paradigmatic model of cue-induced relapse. Preclinical studies have suggested a critical role of the opioid system in modulating Pavlovian–instrumental interactions. The A118G polymorphism of the OPRM1 gene affects opioid receptor availability and function. Furthermore, this polymorphism interacts with cue-induced approach behaviour and is a potential biomarker for pharmacological treatment response in AD. In this study, we tested whether the OPRM1 polymorphism is associated with the PIT effect and relapse in AD. Methods: Using a PIT task, we examined three independent samples: young healthy subjects ( N = 161), detoxified alcohol-dependent patients ( N = 186) and age-matched healthy controls ( N = 105). We used data from a larger study designed to assess the role of learning mechanisms in the development and maintenance of AD. Subjects were genotyped for the A118G (rs1799971) polymorphism of the OPRM1 gene. Relapse was assessed after three months. Results: In all three samples, participants with the minor OPRM1 G-Allele (G+ carriers) showed increased expression of the PIT effect in the absence of learning differences. Relapse was not associated with the OPRM1 polymorphism. Instead, G+ carriers displaying increased PIT effects were particularly prone to relapse. Conclusion: These results support a role for the opioid system in incentive salience motivation. Furthermore, they inform a mechanistic model of aberrant salience processing and are in line with the pharmacological potential of opioid receptor targets in the treatment of AD.

Pilot Study: Texture Analysis of PET Imaging Demonstrates Changes in 18F-FDG Uptake of the Brain After Prophylactic Cranial Irradiation

2020 ◽  
Vol 49 (1) ◽  
pp. 34-38
Author(s):  
David M. Sawyer ◽  
Travis W. Sawyer ◽  
Naghmehossadat Eshghi ◽  
Charles Hsu ◽  
Russell J. Hamilton ◽  
...  
Keyword(s):  
Pilot Study ◽  
Texture Analysis ◽  
Pet Imaging ◽  
Cranial Irradiation ◽  
Prophylactic Cranial Irradiation ◽  
Fdg Uptake ◽  
18F Fdg ◽  
The Brain

scholarly journals The link between inflammation, bugs, the intestine and the brain in alcohol dependence

2017 ◽  
Vol 7 (2) ◽  
pp. e1048-e1048 ◽  
Author(s):  
S Leclercq ◽  
P de Timary ◽  
N M Delzenne ◽  
P Stärkel
Keyword(s):  
Alcohol Dependence ◽  
The Brain

The neuroprotective role of the brain opioid system in stroke injury

2018 ◽  
Vol 23 (7) ◽  
pp. 1385-1395 ◽  
Author(s):  
Bhuvaneshwar Vaidya ◽  
Ali Ehsan Sifat ◽  
Vardan T. Karamyan ◽  
Thomas J. Abbruscato
Keyword(s):  
Opioid System ◽  
The Brain

scholarly journals PET Imaging of [11C]MPC-6827, a Microtubule-Based Radiotracer in Non-Human Primate Brains

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2289
Author(s):  
Naresh Damuka ◽  
Paul Czoty ◽  
Ashley Davis ◽  
Michael Nader ◽  
Susan Nader ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Neurological Disorders ◽  
Healthy Male ◽  
Time Activity ◽  
Positron Emission ◽  
Pet Ct ◽  
Scan Data ◽  
The Brain ◽  
Human Primate

Dysregulation of microtubules is commonly associated with several psychiatric and neurological disorders, including addiction and Alzheimer’s disease. Imaging of microtubules in vivo using positron emission tomography (PET) could provide valuable information on their role in the development of disease pathogenesis and aid in improving therapeutic regimens. We developed [11C]MPC-6827, the first brain-penetrating PET radiotracer to image microtubules in vivo in the mouse brain. The aim of the present study was to assess the reproducibility of [11C]MPC-6827 PET imaging in non-human primate brains. Two dynamic 0–120 min PET/CT imaging scans were performed in each of four healthy male cynomolgus monkeys approximately one week apart. Time activity curves (TACs) and standard uptake values (SUVs) were determined for whole brains and specific regions of the brains and compared between the “test” and “retest” data. [11C]MPC-6827 showed excellent brain uptake with good pharmacokinetics in non-human primate brains, with significant correlation between the test and retest scan data (r = 0.77, p = 0.023). These initial evaluations demonstrate the high translational potential of [11C]MPC-6827 to image microtubules in the brain in vivo in monkey models of neurological and psychiatric diseases.

Effects of the Opioid System Modulator, Samidorphan, on Measures of Alcohol Consumption and Patient-Reported Outcomes in Adults with Alcohol Dependence

2018 ◽  
Vol 42 (10) ◽  
pp. 2011-2021 ◽  
Author(s):  
Stephanie S. O'Malley ◽  
Mark S. Todtenkopf ◽  
Yangchun Du ◽  
Elliot Ehrich ◽  
Bernard L. Silverman
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Dependence ◽  
Patient Reported Outcomes ◽  
Opioid System ◽  
Patient Reported

scholarly journals Relationship of amyloid-β1–42 in blood and brain amyloid: Ginkgo Evaluation of Memory Study

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Oscar L Lopez ◽  
William E Klunk ◽  
Chester A Mathis ◽  
Beth E Snitz ◽  
Yuefang Chang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Pet Imaging ◽  
Standardized Uptake Value ◽  
Amyloid Plaques ◽  
Amyloid Deposition ◽  
Pittsburgh Compound B ◽  
Blood Samples ◽  
Apolipoprotein E4 ◽  
The Brain ◽  
Brain Amyloid Deposition

Abstract A blood test that predicts the extent of amyloid plaques in the brain and risk of Alzheimer’s disease would have important benefits for the early identification of higher risk of dementia and Alzheimer’s disease and the evaluation of new preventative therapies. The goal of this study was to determine whether plasma levels of amyloid-β1–42, 1–40 and the amyloid-β1–42/1–40 ratio among participants in the Pittsburgh centre of the Ginkgo Evaluation of Memory Study were related to the extent of brain fibrillar amyloid plaques measured in 2009 using Pittsburgh compound-B PET imaging, hippocampal volume, cortical thickness in the temporal lobe and white matter lesions. There were 194 participants who had Pittsburgh compound-B measurements in 2009 with the mean age of 85 years; 96% were white and 60% men. Pittsburgh compound-B positivity was defined as a standardized uptake value ratio of ≥1.57. Amyloid-β in blood was measured using a sandwich enzyme-linked immunosorbent assay developed by Eli Lilly and modified at the University of Vermont. All participants were nondemented as of 2008 at the time of study close out. The study sample included 160 with blood samples drawn in 2000–02 and 133 from 2009 and also had brain amyloid measured in 2009. All blood samples were analysed at the same time in 2009. Plasma amyloid-β1–42 was inversely related to the percent Pittsburgh compound-B positive (standardized uptake value ratio ≥1.57), β −0.04, P = 0.005. Practically all participants who were apolipoprotein-E4 positive at older ages were also Pittsburgh compound-B positive for fibrillar amyloid. Among apolipoprotein-E4-negative participants, quartiles of amyloid-β1–42 were inversely related to Pittsburgh compound-B positivity. In multiple regression models, plasma amyloid-β1–42 measured in 2000–02 or 2009 were significantly and inversely related to Pittsburgh compound-B positivity as was the amyloid-β1–42/1–40 ratio. There was a 4-fold increase in the odds ratio for the presence of Pittsburgh compound-B positivity in the brain in 2009 for the first quartile of amyloid-β1–42 as compared with the fourth quartile in the multiple logistic model. This is one of the first longitudinal studies to evaluate the relationship between amyloid-β1–42 in the blood and the extent of brain amyloid deposition measured by PET imaging using Pittsburgh compound-B. Our findings showed that remote and recent low plasma amyloid-β1–42 levels were inversely associated with brain amyloid deposition in cognitively normal individuals. However, changes in plasma amyloid-β1–42 over time (8 years) were small and not related to the amount of Pittsburgh compound-B.

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