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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
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
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
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
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
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
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
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
Deana Haralampieva, Thomas Betzel, Ivana Dinulovic, Souzan Salemi, Meline Stoelting, Stefanie D Krämer, Roger Schibli, Tullio Sulser, Christoph Handschin, Daniel Eberli, Simon M Ametamey
UNLABELLED: Transplantation of human muscle precursor cells (hMPCs) is envisioned for the treatment of various muscle diseases. However, a feasible noninvasive tool to monitor cell survival, migration, and integration into the host tissue is still missing. METHODS: In this study, we designed an adenoviral delivery system to genetically modify hMPCs to express a signaling-deficient form of human dopamine D2 receptor (hD2R). The gene expression levels of the receptor were evaluated by reverse transcriptase polymerase chain reaction, and infection efficiency was evaluated by fluorescent microscopy...
September 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Christopher T Smith, Linh C Dang, Ronald L Cowan, Robert M Kessler, David H Zald
Subjective responses to psychostimulants vary, the basis of which is poorly understood, especially in relation to possible cortical contributions. Here, we tested for relationships between participants' positive subjective responses to oral d-amphetamine (dAMPH) versus placebo and variability in striatal and extrastriatal dopamine (DA) receptor availability and release, measured via positron emission tomography (PET) with the radiotracer (18)F-fallypride. Analyses focused on 35 healthy adult participants showing positive subjective effects to dAMPH measured via the Drug Effects Questionnaire (DEQ) Feel, Like, High, and Want More subscales (Responders), and were repeated after inclusion of 11 subjects who lacked subjective responses...
September 2016: Neuropharmacology
Ping Li, Songbai Gui, Lei Cao, Hua Gao, Jiwei Bai, Chuzhong Li, Yazhuo Zhang
Dopamine receptor-D2 (DRD2) is the most important drug target in prolactinoma. The aim of this current study was to investigate the role of using micro-positron emission tomography (micro-PET) with (18)F-fallypride and (18)F-fluorodeoxyglucose ((18)F-FDG) as molecular imaging tracer in the pituitary glands and prolactinomas of Fischer-344 (F344) rats and detect the difference of the levels of DRD2 in the pituitary glands and prolactinomas of F344 rat prolactinoma models. Female F344 rat prolactinoma models were established by subcutaneous administration of 15 mg 17β-estradiol for 8 weeks...
2016: OncoTargets and Therapy
Zuzana Kasanova, Dennis Hernaus, Thomas Vaessen, Thérèse van Amelsvoort, Oliver Winz, Alexander Heinzel, Jens Pruessner, Felix M Mottaghy, Dina Collip, Inez Myin-Germeys
Early life stress may have a lasting impact on the developmental programming of the dopamine (DA) system implicated in psychosis. Early adversity could promote resilience by calibrating the prefrontal stress-regulatory dopaminergic neurotransmission to improve the individual's fit with the predicted stressful environment. Aberrant reactivity to such match between proximal and distal environments may, however, enhance psychosis disease risk. We explored the combined effects of childhood adversity and adult stress by exposing 12 unmedicated individuals with a diagnosis of non-affective psychotic disorder (NAPD) and 12 healthy controls (HC) to psychosocial stress during an [18F]fallypride positron emission tomography...
2016: PloS One
Michele S Milella, Aryandokht Fotros, Paul Gravel, Kevin F Casey, Kevin Larcher, Jeroen A J Verhaeghe, Sylvia M L Cox, Andrew J Reader, Alain Dagher, Chawki Benkelfat, Marco Leyton
BACKGROUND: Accumulating evidence indicates that drug-related cues can induce dopamine (DA) release in the striatum of substance abusers. Whether these same cues provoke DA release in the human prefrontal cortex remains unknown. METHODS: We used high-resolution positron emission tomography with [18F]fallypride to measure cortical and striatal DA D2/3 receptor availability in the presence versus absence of drug-related cues in volunteers with current cocaine dependence...
August 2016: Journal of Psychiatry & Neuroscience: JPN
Yi-Hua Fa, Jian-Qiang Ni, Xiao-Jin Wu, Jia-Qing Tan, Yi-Wei Wu
The aim of the present study was to investigate the use of (18)F-fallypride micro-positron emission tomography (micro-PET) imaging in the evaluation of the early therapeutic efficacy of L-dopa in the treatment of Parkinson's disease (PD) and the underlying mechanism. (18)F-fallypride was synthesized and its specific binding with dopamine (DA) receptors in normal mouse brain was studied. Following the establishment of a mouse model of PD, the animals were divided into normal control, PD model and L-dopa treatment groups...
January 2016: Experimental and Therapeutic Medicine
Kyoji Okita, Dara G Ghahremani, Doris E Payer, Chelsea L Robertson, Andy C Dean, Mark A Mandelkern, Edythe D London
BACKGROUND: Individuals who use methamphetamine chronically exhibit emotional and dopaminergic neurochemical deficits. Although the amygdala has an important role in emotion processing and receives dopaminergic innervation, little is known about how dopamine transmission in this region contributes to emotion regulation. This investigation aimed to evaluate emotion regulation in subjects who met DSM-IV criteria for methamphetamine dependence, and to test for a relationship between self-reports of difficulty in emotion regulation and D2-type dopamine receptor availability in the amygdala...
April 1, 2016: Drug and Alcohol Dependence
M Kohno, K Okita, A M Morales, C L Robertson, A C Dean, D G Ghahremani, F W Sabb, R A Rawson, M A Mandelkern, R M Bilder, E D London
Stimulant use disorders are associated with deficits in striatal dopamine receptor availability, abnormalities in mesocorticolimbic resting-state functional connectivity (RSFC) and impulsivity. In methamphetamine-dependent research participants, impulsivity is correlated negatively with striatal D2-type receptor availability, and mesocorticolimbic RSFC is stronger than that in controls. The extent to which these features of methamphetamine dependence are interrelated, however, is unknown. This question was addressed in two studies...
November 2016: Molecular Psychiatry
Michael E Ballard, Andy C Dean, Mark A Mandelkern, Edythe D London
BACKGROUND: Dopamine D2/D3 receptor availability in the striatum has been linked with executive function in healthy individuals, and is below control levels among drug addicts, possibly contributing to diminished executive function in the latter group. This study tested for an association of striatal D2/D3 receptor availability with a measure of executive function among research participants who met DSM-IV criteria for methamphetamine dependence. METHODS: Methamphetamine users and non-user controls (n = 18 per group) completed the Wisconsin Card Sorting Test and positron emission tomography with [18F]fallypride...
2015: PloS One
Kyoji Okita, Dara G Ghahremani, Doris E Payer, Chelsea L Robertson, Mark A Mandelkern, Edythe D London
BACKGROUND: Individuals with substance-use disorders exhibit emotional problems, including deficits in emotion recognition and processing, and this class of disorders also has been linked to deficits in dopaminergic markers in the brain. Because associations between these phenomena have not been explored, we compared a group of recently abstinent methamphetamine-dependent individuals (n=23) with a healthy-control group (n=17) on dopamine D2-type receptor availability, measured using positron emission tomography with [(18)F]fallypride...
May 2016: International Journal of Neuropsychopharmacology
Viviane E Bernedo Paredes, Hans-Georg Buchholz, Martin Gartenschläger, Markus Breimhorst, Mathias Schreckenberger, Konrad J Werhahn
OBJECTIVE: Dopamine is an endogenous neuromodulator in cortical circuits and the basal ganglia. In animal models of temporal lobe epilepsy (TLE), seizure threshold is modulated to some extent by dopamine, with D1-receptors having a pro- and D2-receptors an anticonvulsant effect. We aimed to extend our previously reported results on decreased D2/D3 receptor binding in the lateral epileptogenic temporal lobe and to correlate them with demographic and seizure variables to gain a more comprehensive understanding of the underlying involvement of the dopaminergic system in the epileptogenesis of TLE...
2015: PloS One
Chelsea L Robertson, Kenji Ishibashi, Joy Chudzynski, Larissa J Mooney, Richard A Rawson, Brett A Dolezal, Christopher B Cooper, Amira K Brown, Mark A Mandelkern, Edythe D London
Methamphetamine use disorder is associated with striatal dopaminergic deficits that have been linked to poor treatment outcomes, identifying these deficits as an important therapeutic target. Exercise attenuates methamphetamine-induced neurochemical damage in the rat brain, and a preliminary observation suggests that exercise increases striatal D2/D3 receptor availability (measured as nondisplaceable binding potential (BPND)) in patients with Parkinson's disease. The goal of this study was to evaluate whether adding an exercise training program to an inpatient behavioral intervention for methamphetamine use disorder reverses deficits in striatal D2/D3 receptors...
May 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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