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https://www.readbyqxmd.com/read/28884874/cerebral-dopaminergic-and-glutamatergic-transmission-relate-to-different-subjective-responses-of-acute-alcohol-intake-an-in-vivo-multimodal-imaging-study
#1
Gil Leurquin-Sterk, Jenny Ceccarini, Cleo Lina Crunelle, Akila Weerasekera, Bart de Laat, Uwe Himmelreich, Guy Bormans, Koen Van Laere
Converging preclinical evidence links extrastriatal dopamine release and glutamatergic transmission via the metabotropic glutamate receptor 5 (mGluR5) to the rewarding properties of alcohol. To date, human evidence is lacking on how and where in the brain these processes occur. Mesocorticolimbic dopamine release upon intravenous alcohol administration and mGluR5 availability were measured in 11 moderate social drinkers by single-session [(18) F]fallypride and [(18) F]FPEB positron emission tomography, respectively...
September 8, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28858444/a-population-approach-to-guide-amisulpride-dose-adjustments-in-older-patients-with-alzheimer-s-disease
#2
Suzanne Reeves, Julie Bertrand, Emma McLachlan, Fabrizia D'Antonio, Stuart Brownings, Akshay Nair, Suki Greaves, Alan Smith, Joel T Dunn, Paul Marsden, Robert Kessler, Hiroyuki Uchida, David Taylor, Robert Howard
OBJECTIVE: We have previously reported high dopamine D2/3 receptor occupancies at low amisulpride concentrations in older people with Alzheimer's disease (AD), during off-label treatment of AD-related psychosis. This post hoc analysis explored pharmacokinetic (concentration) and pharmacodynamic (prolactin, D2/3 occupancy) contributions to symptom reduction and extrapyramidal side effects (EPS) to inform AD-specific dose adjustments. METHODS: Population pharmacokinetic-pharmacodynamic models were developed by combining pharmacokinetic data from a phase 1 study in 20 healthy older people with pharmacokinetic prolactin, [¹⁸F]fallypride D2/3 receptor imaging, and clinical outcome data from 28 older patients prescribed open amisulpride (25-75 mg/d) to treat AD-related psychosis...
July 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28857231/challenges-in-the-development-of-dopamine-d2-and-d3-selective-radiotracers-for-pet-imaging-studies
#3
Robert H Mach, Robert R Luedtke
The dopamine D2-like receptors (i.e., D2/3 receptors) have been the most extensively studied CNS receptor with PET. The three different radiotracers which have been used in these studies are [(11) C]raclopride, [(18) F]fallypride, and [(11) C]PHNO. Since these radiotracers have a high affinity for both dopamine D2 and D3 receptors, the density of dopamine receptors in the CNS is reported as the D2/3 binding potential, which reflects a measure of the density of both receptor subtypes. Although the development of D2- and D3-selective PET radiotracers has been an active area of research for many years, this by and large presents an unmet need in the area of translational PET imaging studies...
August 31, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28818716/positron-emission-tomography-pet-imaging-of-nicotine-induced-dopamine-release-in-squirrel-monkeys-using-18-f-fallypride
#4
Jennifer E Naylor, Takato Hiranita, Katelin S Matazel, Xuan Zhang, Merle G Paule, Amy K Goodwin
BACKGROUND: Nicotine, the principal psychoactive tobacco constituent, is thought to produce its reinforcing effects via actions within the mesolimbic dopamine (DA) system. The objective of the current study was to examine the effect of nicotine on DA D2/D3 receptor availability in the nonhuman primate brain with the use of the radioligand [(18)F]fallypride and positron emission tomography (PET). METHODS: Ten adult male squirrel monkeys were used in the current study...
August 8, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28816571/effects-of-flow-changes-on-radiotracer-binding-simultaneous-measurement-of-neuroreceptor-binding-and-cerebral-blood-flow-modulation
#5
Christin Y Sander, Joseph B Mandeville, Hsiao-Ying Wey, Ciprian Catana, Jacob M Hooker, Bruce R Rosen
The potential effects of changes in blood flow on the delivery and washout of radiotracers has been an ongoing question in PET bolus injection studies. This study provides practical insight into this topic by experimentally measuring cerebral blood flow (CBF) and neuroreceptor binding using simultaneous PET/MRI. Hypercapnic challenges (7% CO2) were administered to non-human primates in order to induce controlled increases in CBF, measured with pseudo-continuous arterial spin labeling. Simultaneously, dopamine D2/D3 receptor binding of [(11)C]raclopride or [(18)F]fallypride was monitored with dynamic PET...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28700819/posterior-dopamine-d2-3-receptors-and-brain-network-functional-connectivity
#6
Atsuko Nagano-Saito, Jennifer I Lissemore, Paul Gravel, Marco Leyton, Felix Carbonell, Chawki Benkelfat
Recent studies suggest that dopaminergic tone influences resting state activity in multiple brain networks. Although dopamine receptors and transporters have been identified in the posteromedial and parietal cortices, which are linked to functional networks such as the default mode network (DMN), the relationship between dopamine receptor distribution in these posterior regions and resting-state connectivity has yet to be explored. Here, we used a multi-modal neuroimaging strategy, combining resting-state functional magnetic resonance imaging (rsfMRI) and [18 F]-fallypride high-resolution positron emission tomography (PET), to examine the association between within-network functional connectivity and the dopamine D2/3 receptor distribution in the posterior portion of the brain in 13 healthy adults...
July 12, 2017: Synapse
https://www.readbyqxmd.com/read/28664927/low-striatal-dopamine-d2-type-receptor-availability-is-linked-to-simulated-drug-choice-in-methamphetamine-users
#7
Scott J Moeller, Kyoji Okita, Chelsea L Robertson, Michael E Ballard, Anna B Konova, Rita Z Goldstein, Mark A Mandelkern, Edythe D London
Individuals with drug use disorders seek drugs over other rewarding activities, and exhibit neurochemical deficits related to dopamine, which is involved in value-based learning and decision-making. Thus, a dopaminergic disturbance may underpin drug-biased choice in addiction. Classical drug-choice assessments, which offer drug-consumption opportunities, are inappropriate for addicted individuals seeking treatment or abstaining. Fifteen recently abstinent methamphetamine users and 15 healthy controls completed two laboratory paradigms of 'simulated' drug choice (choice for drug-related versus affectively pleasant, unpleasant, and neutral images), and underwent positron emission tomography measurements of dopamine D2-type receptor availability, indicated by binding potential (BPND) for [(18)F]fallypride...
June 30, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28643852/therapeutic-d2-3-receptor-occupancies-and-response-with-low-amisulpride-blood-concentrations-in-very-late-onset-schizophrenia-like-psychosis-vloslp
#8
Suzanne Reeves, Kate Eggleston, Elizabeth Cort, Emma McLachlan, Stuart Brownings, Akshay Nair, Suki Greaves, Alan Smith, Joel Dunn, Paul Marsden, Robert Kessler, David Taylor, Julie Bertrand, Robert Howard
OBJECTIVE: Antipsychotic drug sensitivity in very late-onset schizophrenia-like psychosis (VLOSLP) is well documented, but poorly understood. This study aimed to investigate blood drug concentration, D2/3 receptor occupancy and outcome in VLOSLP during open amisulpride prescribing, and compare this with Alzheimer's disease (AD). METHODS: Blood drug concentration, prolactin, symptoms and extrapyramidal side-effects (EPS) were serially assessed during dose titration...
June 23, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28623450/the-relationship-between-excitement-symptom-severity-and-extrastriatal-dopamine-d2-3-receptor-availability-in-patients-with-schizophrenia-a-high-resolution-pet-study-with-18-f-fallypride
#9
Yo-Han Joo, Jeong-Hee Kim, Young-Don Son, Hang-Keun Kim, Yeon-Jeong Shin, Sang-Yoon Lee, Jong-Hoon Kim
The purpose of this study was to investigate the relationship between specific symptom severity and D2/3 receptor availability in extrastriatal regions in outpatients with schizophrenia to shed light on the role of extrastriatal dopaminergic neurotransmission in the pathophysiology of symptoms of schizophrenia. Sixteen schizophrenia patients receiving relatively low-dose maintenance atypical antipsychotics and seventeen healthy controls underwent 3-Tesla magnetic resonance imaging and high-resolution positron emission tomography with [(18)F]fallypride...
June 16, 2017: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/28599133/dose-on-demand-production-of-diverse-18-f-radiotracers-for-preclinical-applications-using-a-continuous-flow-microfluidic-system
#10
Lidia Matesic, Annukka Kallinen, Ivan Greguric, Giancarlo Pascali
INTRODUCTION: The production of (18)F-radiotracers using continuous flow microfluidics is under-utilized due to perceived equipment limitations. We describe the dose-on-demand principle, whereby the back-to-back production of multiple, diverse (18)F-radiotracers can be prepared on the same day, on the same microfluidic system using the same batch of [(18)F]fluoride, the same microreactor, the same HPLC column and SPE cartridge to obtain a useful production yield. METHODS: [(18)F]MEL050, [(18)F]Fallypride and [(18)F]PBR111 were radiolabeled with [(18)F]fluoride using the Advion NanoTek Microfluidic Synthesis System...
September 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28576546/d2-d3-dopamine-receptor-binding-with-f-18-fallypride-correlates-of-executive-function-in-medication-na%C3%A3-ve-patients-with-schizophrenia
#11
Nora S Vyas, Monte S Buchsbaum, Douglas S Lehrer, Brian M Merrill, Alex DeCastro, Nicholas A Doninger, Bradley T Christian, Jogeshwar Mukherjee
Converging evidence indicates that the prefrontal cortex is critically involved in executive control and that executive dysfunction is implicated in schizophrenia. Reduced dopamine D2/D3 receptor binding potential has been reported in schizophrenia, and the correlations with neuropsychological test scores have been positive and negative for different tasks. The aim of this study was to examine the relation between dopamine D2/D3 receptor levels with frontal and temporal neurocognitive performance in schizophrenia...
May 30, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28461214/striatal-dopaminergic-modulation-of-reinforcement-learning-predicts-reward-oriented-behavior-in-daily-life
#12
Zuzana Kasanova, Jenny Ceccarini, Michael J Frank, Thérèse van Amelsvoort, Jan Booij, Alexander Heinzel, Felix Mottaghy, Inez Myin-Germeys
Much human behavior is driven by rewards. Preclinical neurophysiological and clinical positron emission tomography (PET) studies have implicated striatal phasic dopamine (DA) release as a primary modulator of reward processing. However, the relationship between experimental reward-induced striatal DA release and responsiveness to naturalistic rewards, and therefore functional relevance of these findings, has been elusive. We therefore combined, for the first time, a DA D2/3 receptor [(18)F]fallypride PET during a probabilistic reinforcement learning (RL) task with a six day ecological momentary assessments (EMA) of reward-related behavior in the everyday life of 16 healthy volunteers...
April 29, 2017: Biological Psychology
https://www.readbyqxmd.com/read/28398340/the-impact-of-common-dopamine-d2-receptor-gene-polymorphisms-on-d2-3-receptor-availability-c957t-as-a-key-determinant-in-putamen-and-ventral-striatum
#13
C T Smith, L C Dang, J W Buckholtz, A M Tetreault, R L Cowan, R M Kessler, D H Zald
Dopamine function is broadly implicated in multiple neuropsychiatric conditions believed to have a genetic basis. Although a few positron emission tomography (PET) studies have investigated the impact of single-nucleotide polymorphisms (SNPs) in the dopamine D2 receptor gene (DRD2) on D2/3 receptor availability (binding potential, BPND), these studies have often been limited by small sample size. Furthermore, the most commonly studied SNP in D2/3 BPND (Taq1A) is not located in the DRD2 gene itself, suggesting that its linkage with other DRD2 SNPs may explain previous PET findings...
April 11, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28334978/therapeutic-window-of-dopamine-d2-3-receptor-occupancy-to-treat-psychosis-in-alzheimer-s-disease
#14
Suzanne Reeves, Emma McLachlan, Julie Bertrand, Fabrizia D Antonio, Stuart Brownings, Akshay Nair, Suki Greaves, Alan Smith, David Taylor, Joel Dunn, Paul Marsden, Robert Kessler, Robert Howard
See Caravaggio and Graff-Guerrero (doi:10.1093/awx023) for a scientific commentary on this article.Antipsychotic drugs, originally developed to treat schizophrenia, are used to treat psychosis, agitation and aggression in Alzheimer's disease. In the absence of dopamine D2/3 receptor occupancy data to inform antipsychotic prescribing for psychosis in Alzheimer's disease, the mechanisms underpinning antipsychotic efficacy and side effects are poorly understood. This study used a population approach to investigate the relationship between amisulpride blood concentration and central D2/3 occupancy in older people with Alzheimer's disease by combining: (i) pharmacokinetic data (280 venous samples) from a phase I single (50 mg) dose study in healthy older people (n = 20, 65-79 years); (ii) pharmacokinetic, 18F-fallypride D2/3 receptor imaging and clinical outcome data on patients with Alzheimer's disease who were prescribed amisulpride (25-75 mg daily) to treat psychosis as part of an open study (n = 28; 69-92 years; 41 blood samples, five pretreatment scans, 19 post-treatment scans); and (iii) 18F-fallypride imaging of an antipsychotic free Alzheimer's disease control group (n = 10, 78-92 years), to provide additional pretreatment data...
April 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28089678/reduced-effects-of-age-on-dopamine-d2-receptor-levels-in-physically-active-adults
#15
Linh C Dang, Jaime J Castrellon, Scott F Perkins, Nam T Le, Ronald L Cowan, David H Zald, Gregory R Samanez-Larkin
Physical activity has been shown to ameliorate dopaminergic degeneration in non-human animal models. However, the effects of regular physical activity on normal age-related changes in dopamine function in humans are unknown. Here we present cross-sectional data from forty-four healthy human subjects between 23 and 80 years old, showing that typical age-related dopamine D2 receptor loss, assessed with PET [18F]fallypride, was significantly reduced in physically active adults compared to less active adults.
March 1, 2017: NeuroImage
https://www.readbyqxmd.com/read/27634830/cigarette-use-and-striatal-dopamine-d2-3-receptors-possible-role-in-the-link-between-smoking-and-nicotine-dependence
#16
Kyoji Okita, Mark A Mandelkern, Edythe D London
BACKGROUND: Cigarette smoking induces dopamine release in the striatum, and smoking- or nicotine-induced ventral striatal dopamine release is correlated with nicotine dependence. Smokers also exhibit lower dopamine D2/3 receptor availability in the dorsal striatum than nonsmokers. Negative correlations of striatal dopamine D2/3 receptor availability with smoking exposure and nicotine dependence, therefore, might be expected but have not been tested. METHODS: Twenty smokers had positron emission tomography scans with [(18)F]fallypride to measure dopamine D2/3 receptor availability in ventral and dorsal regions of the striatum and provided self-report measures of recent and lifetime smoking and of nicotine dependence...
November 2016: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27408789/occupancy-of-pramipexole-sifrol-at-cerebral-dopamine-d2-3-receptors-in-parkinson-s-disease-patients
#17
Angela Deutschländer, Christian la Fougère, Kai Boetzel, Nathalie L Albert, Franz-Josef Gildehaus, Peter Bartenstein, Guoming Xiong, Paul Cumming
Whereas positron emission tomography (PET) with the antagonist ligand [(18)F]fallypride reveals the composite of dopamine D2 and D3 receptors in brain, treatment of Parkinson's disease (PD) patients with the D3-prefering agonist pramipexole should result in preferential occupancy in the nucleus accumbens, where the D3-subtype is most abundant. To test this prediction we obtained pairs of [(18)F]fallypride PET recordings in a group of nine PD patients, first in a condition of treatment as usual with pramipexole (ON-Sifrol; 3 × 0...
2016: NeuroImage: Clinical
https://www.readbyqxmd.com/read/27396374/acute-effect-of-intravenously-applied-alcohol-in-the-human-striatal-and-extrastriatal-d2-d3-dopamine-system
#18
Philippe Pfeifer, Oliver Tüscher, Hans Georg Buchholz, Gerhard Gründer, Ingo Vernaleken, Michael Paulzen, Ulrich S Zimmermann, Stephan Maus, Klaus Lieb, Thomas Eggermann, Christoph Fehr, Mathias Schreckenberger
Investigations on the acute effects of alcohol in the human mesolimbic dopamine D2 /D3 receptor system have yielded conflicting results. With respect to the effects of alcohol on extrastriatal D2 /D3 dopamine receptors no investigations have been reported yet. Therefore we applied PET imaging using the postsynaptic dopamine D2 /D3 receptor ligand [(18) F]fallypride addressing the question, whether intravenously applied alcohol stimulates the extrastriatal and striatal dopamine system. We measured subjective effects of alcohol and made correlation analyses with the striatal and extrastriatal D2 /D3 binding potential...
July 11, 2016: Addiction Biology
https://www.readbyqxmd.com/read/27329684/sex-differences-in-midbrain-dopamine-d2-type-receptor-availability-and-association-with-nicotine-dependence
#19
Kyoji Okita, Nicole Petersen, Chelsea L Robertson, Andy C Dean, Mark A Mandelkern, Edythe D London
Women differ from men in smoking-related behaviors, among them a greater difficulty in quitting smoking. Unlike female smokers, male smokers have lower striatal dopamine D2-type receptor availability (binding potential, BPND) than nonsmokers and exhibit greater smoking-induced striatal dopamine release. Because dopamine D2-type autoreceptors in the midbrain influence striatal dopamine release, a function that has been linked to addiction, we tested for sex differences in midbrain dopamine D2-type receptor BPND and in relationships between midbrain BPND, nicotine dependence and striatal dopamine D2-type receptor BPND...
November 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27208860/associations-between-dopamine-d2-receptor-availability-and-bmi-depend-on-age
#20
Linh C Dang, Gregory R Samanez-Larkin, Jaime J Castrellon, Scott F Perkins, Ronald L Cowan, David H Zald
OBJECTIVE: The dopamine D2/3 receptor subtypes (DRD2/3) are the most widely studied neurotransmitter biomarker in research on obesity, but results to date have been inconsistent, have typically involved small samples, and have rarely accounted for subjects' ages despite the large impact of age on DRD2/3 levels. We aimed to clarify the relation between DRD2/3 availability and BMI by examining this association in a large sample of subjects with BMI spanning the continuum from underweight to extremely obese...
September 2016: NeuroImage
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