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https://www.readbyqxmd.com/read/29128393/rem-sleep-deprivation-and-dopaminergic-d2-receptors-modulation-increase-recognition-memory-in-an-animal-model-of-parkinson-s-disease
#1
Adriano D S Targa, Ana Carolina D Noseda, Lais S Rodrigues, Mariana F Aurich, Marcelo M S Lima
Cognitive impairment is an important non-motor symptom of Parkinson's disease (PD). The neuronal death in nigrostriatal pathway is the main factor for motor symptoms and recent studies indicate a possible influence in non-motor symptoms as well. The pedunculopontine tegmental nucleus (PPT) and basal ganglia are closely related anatomically and functionally and, since they are affected by neurodegeneration in PD, they might be involved in recognition memory. To investigate this, we promoted an ibotenic acid lesion within the PPT or a rotenone lesion within substantia nigra pars compacta (SNpc) of Wistar rats, followed by 24h of REM sleep deprivation (REMSD)...
November 8, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29112197/association-of-genetic-ancestry-with-striatal-dopamine-d2-d3-receptor-availability
#2
C E Wiers, P C Towb, C A Hodgkinson, P-H Shen, C Freeman, G Miller, E Lindgren, E Shokri-Kojori, Ş B Demiral, S W Kim, D Tomasi, H Sun, G-J Wang, D Goldman, N D Volkow
Despite ethnic differences in allele frequencies of variants in dopaminergic genes associated with dopamine D2/D3 receptor availability (D2R), no study to date has investigated the relationship between genetic ancestry and striatal D2R. Here, we show that ancestry-informative markers significantly predict dorsal striatal D2R in 117 healthy ethnically diverse residents of the New York metropolitan area using Positron Emission Tomography (PET) with [(11)C]raclopride (P<0.0001), while correcting for age, sex, BMI, education, smoking status, and estimated socioeconomic status (ZIP codes)...
November 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29106979/development-of-a-population-pharmacokinetic-model-to-predict-brain-distribution-and-dopamine-d2-receptor-occupancy-of-raclopride-in-non-anesthetized-rat
#3
Yin Cheong Wong, Trayana Ilkova, Rob C van Wijk, Robin Hartman, Elizabeth C M de Lange
BACKGROUND: Raclopride is a selective antagonist of the dopamine D2 receptor. It is one of the most frequently used in vivo D2 tracers (at low doses) for assessing drug-induced receptor occupancy (RO) in animals and humans. It is also commonly used as a pharmacological blocker (at high doses) to occupy the available D2 receptors and antagonize the action of dopamine or drugs on D2 in preclinical studies. The aims of this study were to comprehensively evaluate its pharmacokinetic (PK) profiles in different brain compartments and to establish a PK-RO model that could predict the brain distribution and RO of raclopride in the freely moving rat using a LC-MS based approach...
November 4, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29106549/the-in-vitro-actions-of-loxapine-on-dopaminergic-and-serotonergic-receptors-time-to-consider-atypical-classification-of-this-antipsychotic-drug
#4
Florian Ferreri, Dominique Drapier, Emmanuelle Baloche, Mehemed Ouzid, Luc Zimmer, Pierre-Michel Llorca
Background: The denomination of typical antipsychotic for loxapine has poor relation to current knowledge of the molecule's relevant modes of action. Method: Competition binding experiments were performed on expressed human recombinant receptors in CHO cells and HEK-293 cells for D1 to D5, 5-HT1A, 5-HT2A, 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro autoradiographies using [ 11C]-Raclopride [18F]-Altanserin [18F]-MPPF [11C]-SB207145 and [18F]-2FNQ1P were measured in brain tissue of a male primate followed by addition of increasing doses of loxapine succinate...
November 2, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29071465/toward-whole-brain-dopamine-movies-a-critical-review-of-pet-imaging-of-dopamine-transmission-in-the-striatum-and-cortex
#5
Heather Liu, Yasmin Zakiniaeiz, Kelly P Cosgrove, Evan D Morris
The mesocorticolimbic dopamine (DA) circuit, comprising the mesolimbic and mesocortical DA pathways, plays a crucial role in reward, cognitive control, and motivation. The positron emission tomography (PET) radiotracer, [C-11]raclopride, has been used widely to image DA receptors and DA changes in the mesolimbic pathway before and after pharmacological and behavioral challenges. In certain circumstances, properties of traditional kinetic models-used to analyze dynamic PET data-are not well-suited to describing the effects of stimulus-induced DA release...
October 25, 2017: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/29071217/modafinil-improves-catalepsy-in-a-rat-6-hydroxydopamine-model-of-parkinson-s-disease-possible-involvement-of-dopaminergic-neurotransmission
#6
Reza Vajdi-Hokmabad, Mojtaba Ziaee, Saeed Sadigh-Eteghad, Siamak Sandoghchian Shotorbani, Javad Mahmoudi
Purpose: Modafinil is a vigilance-enhancing drug licensed for narcolepsy. The use of modafinil leads to various neuromodulatory effects with very low abuse potential. A body of evidence suggested that modafinil may have anti-parkinsonian effects. This study was designed to evaluate whether modafinil could improve motor dysfunction in the 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease. Methods: Male Wistar rats (180-220 g, n= 98) were used in this study. Parkinsonism was induced by injection of 6-hydroxydopamine (10 μg/2μl in 0...
September 2017: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29035918/dopaminergic-mechanisms-in-periaqueductal-gray-mediated-antinociception
#7
Glaucia Tobaldini, Rafael A Reis, Natalia F Sardi, Mayla K Lazzarim, Dabna H Tomim, Marcelo M S Lima, Luana Fischer
As important as perceiving pain is the ability to modulate this perception in some contextual salient situations. The periaqueductal gray (PAG) is perhaps the most important site of endogenous pain modulation; however, little is known about dopaminergic mechanisms underlying PAG-mediated antinociception. In this study, we used a pharmacological approach to evaluate this subject. We found that µ-opioid receptor-induced antinociception (DAMGO, 0.3 μg) from PAG was blocked by the coadministration of either D1-like or D2-like dopaminergic antagonists (SCH23390, 2, 4, and 6 μg or raclopride, 2 and 4 μg, respectively) both in the tail-flick and in the mechanical paw-withdrawal test...
October 13, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/29028935/latent-profile-analysis-reveals-behavioral-and-brain-correlates-of-dopamine-cognition-associations
#8
Martin Lövdén, Nina Karalija, Micael Andersson, Anders Wåhlin, Jan Axelsson, Ylva Köhncke, Lars S Jonasson, Anna Rieckman, Goran Papenberg, Douglas D Garrett, Marc Guitart-Masip, Alireza Salami, Katrine Riklund, Lars Bäckman, Lars Nyberg, Ulman Lindenberger
Evidence suggests that associations between the neurotransmitter dopamine and cognition are nonmonotonic and open to modulation by various other factors. The functional implications of a given level of dopamine may therefore differ from person to person. By applying latent-profile analysis to a large (n = 181) sample of adults aged 64-68 years, we probabilistically identified 3 subgroups that explain the multivariate associations between dopamine D2/3R availability (probed with 11C-raclopride-PET, in cortical, striatal, and hippocampal regions) and cognitive performance (episodic memory, working memory, and perceptual speed)...
September 25, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29016872/affinity-states-of-striatal-dopamine-d2-receptors-in-antipsychotic-free-patients-with-schizophrenia
#9
Manabu Kubota, Tomohisa Nagashima, Harumasa Takano, Fumitoshi Kodaka, Hironobu Fujiwara, Keisuke Takahata, Sho Moriguchi, Yasuyuki Kimura, Makoto Higuchi, Yoshiro Okubo, Hidehiko Takahashi, Hiroshi Ito, Tetsuya Suhara
Background: Dopamine D2 receptors are reported to have high-affinity (D2High) and low-affinity (D2Low) states. Although an increased proportion of D2High has been demonstrated in animal models of schizophrenia, few clinical studies have investigated this alteration of D2High in schizophrenia in vivo. Methods: Eleven patients with schizophrenia, including 10 antipsychotic-naive and 1 antipsychotic-free individuals, and 17 healthy controls were investigated. Psychopathology was assessed by Positive and Negative Syndrome Scale, and a 5-factor model was used...
November 1, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28953191/nucleus-accumbens-mediates-the-pronociceptive-effect-of-sleep-deprivation-the-role-of-adenosine-a2a-and-dopamine-d2-receptors
#10
Natalia Fantin Sardi, Glaucia Tobaldini, Rosana Nogueira Morais, Luana Fischer
Sleep disorders increase pain sensitivity and the risk of developing painful conditions; however, the underlying mechanisms are poorly understood. It has been suggested that nucleus accumbens (NAc) influences sleep-wake cycle by means of a balance between adenosine activity at A2A receptors and dopamine activity at D2 receptors. Because the NAc also plays an important role in pain modulation, we hypothesized that the NAc and its A2A and D2 receptors mediate the pronociceptive effect of rapid eye movement (REM) sleep deprivation (SD)...
September 25, 2017: Pain
https://www.readbyqxmd.com/read/28921163/discriminative-stimulus-properties-of-the-atypical-antipsychotic-amisulpride-comparison-to-its-isomers-and-to-other-benzamide-derivatives-antipsychotic-antidepressant-and-antianxiety-drugs-in-c57bl-6-mice
#11
Timothy J Donahue, Todd M Hillhouse, Kevin A Webster, Richard Young, Eliseu O De Oliveira, Joseph H Porter
RATIONALE: Racemic (RS)-amisulpride (Solian(®)) is an atypical antipsychotic drug used to treat schizophrenia and dysthymia. Blockade of dopamine D2/D3 and/or serotonin 5-HT7 receptors is implicated in its pharmacological effects. While the (S)-amisulpride isomer possesses a robust discriminative cue, discriminative stimulus properties of (RS)-amisulpride have not been evaluated. OBJECTIVES: The present study established (RS)-amisulpride as a discriminative stimulus and assessed amisulpride-like effects of amisulpride stereoisomers, other benzamide derivatives, and antipsychotic, antidepressant, and anxiolytic drugs...
December 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28916921/potential-effect-of-prolonged-sevoflurane-anesthesia-on-the-kinetics-of-11-c-raclopride-in-non-human-primates
#12
Ryosuke Arakawa, Lars Farde, Junya Matsumoto, Naoki Kanegawa, Igor Yakushev, Kai-Chun Yang, Akihiro Takano
PURPOSE: Positron emission tomography (PET) in non-human primates (NHP) is commonly performed under anesthesia, with sevoflurane being a widely used inhaled anesthetic. PET measurement in NHP can be repeated, and a difference in radioligand kinetics has previously been observed between the first and second PET measurement on the same day using sevoflurane anesthesia. In this study, we evaluated the effect of prolonged sevoflurane anesthesia on kinetics and binding potential (BPND) of [(11)C]raclopride in NHP...
September 15, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28895569/the-effects-of-the-monoamine-stabilizer-osu6162-on-binge-like-eating-and-cue-controlled-food-seeking-behavior-in-rats
#13
Kristin Feltmann, Chiara Giuliano, Barry J Everitt, Pia Steensland, Johan Alsiö
Binge-eating disorder (BED) is characterized by recurring episodes of excessive consumption of palatable food and an increased sensitivity to food cues. Patients with BED display an addiction-like symptomatology and the dopamine system might be a potential treatment target. The clinically safe monoamine stabilizer (-)-OSU6162 (OSU6162) restores dopaminergic dysfunction in long-term alcohol-drinking rats and shows promise as a novel treatment for alcohol use disorder. Here, the effects of OSU6162 on consummatory (binge-like eating) and appetitive (cue-controlled seeking) behavior motivated by chocolate-flavored sucrose pellets were evaluated in non-food-restricted male Lister Hooded rats...
September 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28879087/chronic-exposure-to-dopamine-agonists-affects-the-integrity-of-striatal-d2-receptors-in-parkinson-s-patients
#14
Marios Politis, Heather Wilson, Kit Wu, David J Brooks, Paola Piccini
We aimed to investigate the integrity and clinical relevance of striatal dopamine receptor type-2 (D2R) availability in Parkinson's disease (PD) patients. We studied 68 PD patients, spanning from early to advanced disease stages, and 12 healthy controls. All participants received one [(11)C]raclopride PET scan in an OFF medication condition for quantification of striatal D2R availability in vivo. Parametric images of [(11)C]raclopride non-displaceable binding potential were generated from the dynamic [(11)C]raclopride scans using implementation of the simplified reference tissue model with cerebellum as the reference tissue...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28878639/differential-associations-between-cortical-thickness-and-striatal-dopamine-in-treatment-na%C3%A3-ve-adults-with-adhd-vs-healthy-controls
#15
Mariya V Cherkasova, Nazlie Faridi, Kevin F Casey, Kevin Larcher, Gillian A O'Driscoll, Lily Hechtman, Ridha Joober, Glen B Baker, Jennifer Palmer, Alan C Evans, Alain Dagher, Chawki Benkelfat, Marco Leyton
Alterations in catecholamine signaling and cortical morphology have both been implicated in the pathophysiology of attention deficit/hyperactivity disorder (ADHD). However, possible links between the two remain unstudied. Here, we report exploratory analyses of cortical thickness and its relation to striatal dopamine transmission in treatment-naïve adults with ADHD and matched healthy controls. All participants had one magnetic resonance imaging (MRI) and two [(11)C]raclopride positron emission tomography scans...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28870629/microinjection-of-the-dopamine-d2-receptor-antagonist-raclopride-into-the-medial-preoptic-area-reduces-rem-sleep-in-lactating-rats
#16
Luciana Benedetto, Mayda Rivas, Matias Cavelli, Florencia Peña, Jaime Monti, Annabel Ferreira, Pablo Torterolo
The medial preoptic area (mPOA) is a brain structure classically related to both non-REM (NREM) sleep and maternal behavior. Although the dopaminergic system is known to play a role in the control of the states of sleep and wakefulness, its effects within the mPOA on sleep are still not clear. Microinjection of the dopamine D2 receptor antagonist Raclopride into the mPOA has been shown to promote nursing postures in lactating dams with no effects on active maternal behavior. We hypothesized that the facilitation of nursing postures may be also associated with the promotion of NREM sleep...
October 17, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28870407/striatal-dopamine-d2-3-receptor-mediated-neurotransmission-in-major-depression-implications-for-anhedonia-anxiety-and-treatment-response
#17
Marta Peciña, Magdalena Sikora, Erich T Avery, Joseph Heffernan, Susana Peciña, Brian J Mickey, Jon-Kar Zubieta
Dopamine (DA) neurotransmission within the brain's reward circuit has been implicated in the pathophysiology of depression and in both, cognitive and pharmacological mechanisms of treatment response. Still, a direct relationship between measures of DA neurotransmission and reward-related deficits in patients with depression has not been demonstrated. To gain insight into the symptom-specific alterations in the DA system in patients with depression, we used positron emission tomography (PET) and the D2/3 receptor-selective radiotracer [(11)C]raclopride in twenty-three non-smoking un-medicated Major Depressive Disorder (MDD) patients and sixteen healthy controls (HC)...
October 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28857231/challenges-in-the-development-of-dopamine-d2-and-d3-selective-radiotracers-for-pet-imaging-studies
#18
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/28822101/revisiting-the-logan-plot-to-account-for-non-negligible-blood-volume-in-brain-tissue
#19
Martin Schain, Patrik Fazio, Ladislav Mrzljak, Nahid Amini, Nabil Al-Tawil, Cheryl Fitzer-Attas, Juliana Bronzova, Bernhard Landwehrmeyer, Christina Sampaio, Christer Halldin, Andrea Varrone
BACKGROUND: Reference tissue-based quantification of brain PET data does not typically include correction for signal originating from blood vessels, which is known to result in biased outcome measures. The bias extent depends on the amount of radioactivity in the blood vessels. In this study, we seek to revisit the well-established Logan plot and derive alternative formulations that provide estimation of distribution volume ratios (DVRs) that are corrected for the signal originating from the vasculature...
August 18, 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28816571/effects-of-flow-changes-on-radiotracer-binding-simultaneous-measurement-of-neuroreceptor-binding-and-cerebral-blood-flow-modulation
#20
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
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