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Deana Haralampieva, Souzan Salemi, Thomas Betzel, Ivana Dinulovic, Stefanie D Krämer, Roger Schibli, Tullio Sulser, Christoph Handschin, Simon M Ametamey, Daniel Eberli
While many groups demonstrated new muscle tissue formation after muscle precursor cell (MPC) injection, the capacity of these cells to heal muscle damage, for example, sphincter in stress urinary incontinence, in long-term is still limited. Therefore, the first goal of our project was to optimize the functional regenerative potential of hMPC by genetic modification to overexpress human peroxisome proliferator-activated receptor gamma coactivator 1-alpha (hPGC-1 α ), key regulator of exercise-mediated adaptation...
2018: Stem Cells International
Josué O Suárez-Ortiz, Felipe Cortés-Salazar, Ariadna L Malagón-Carrillo, Verónica E López-Alonso, Juan M Mancilla-Díaz, Juan G Tejas-Juárez, Rodrigo E Escartín-Pérez
Overeating is one of the most relevant clinical features in Binge Eating Disorder and in some obesity patients. According to several studies, alterations in the mesolimbic dopaminergic transmission produced by non-homeostatic feeding behavior may be associated with changes in the reward system similar to those produced by drugs of abuse. Although it is known that binge-eating is related with changes in dopaminergic transmission mediated by D2 receptors in the nucleus accumbens shell (NAcS), it has not been determined whether these receptors may be a potential target for the treatment of eating pathology with binge-eating...
2018: Frontiers in Neuroscience
Justin N Siemian, Shushan Jia, Jian-Feng Liu, Yanan Zhang, Jun-Xu Li
Chronic pain is a significant public health problem with a lack of safe and effective analgesics. The imidazoline I2 receptor (I2 R) is a promising analgesic target, but the neuroanatomical structures involved in mediating I2 R-associated behaviors are unknown. I2 Rs are enriched in the arcuate nucleus, dorsal raphe (DR), interpeduncular nucleus, lateral mammillary body, medial habenula, nucleus accumbens (NAc), and paraventricular nucleus, thus this study investigated the antinociceptive and hypothermic effects of microinjections of the I2 R agonist 2-(2-benzofuranyl)-2-imidazoline hydrochloride (2-BFI)...
March 7, 2018: European Journal of Neuroscience
Dana Mayer, Evelyn Kahl, Taygun C Uzuneser, Markus Fendt
The relief from an aversive event is rewarding. Since organisms are able to learn which environmental cues can cease an aversive event, relief learning helps to better cope with future aversive events. Literature data suggest that relief learning is affected in various psychopathological conditions, such as anxiety disorders. Here, we investigated the role of the mesolimbic dopamine system in relief learning. Using a relief learning procedure in Sprague Dawley rats, we applied a combination of behavioral experiments with anatomical tracing, c-Fos immunohistochemistry, and local chemogenetic and pharmacological interventions to broadly characterize the role of the mesolimbic dopamine system...
February 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
José M Benlloch, Antonio J González, Roberto Pani, Enrico Preziosi, Carl Jackson, John Murphy, Julio Barberá, Carlos Correcher, Sebastian Aussenhofer, Daniel Gareis, Dimitris Visvikis, Julien Bert, Bengt Langstrom, Lars Farde, Miklos Toth, Jenny Haggkvist, Fabio V Caixeta, Klas Kullander, Ian Somlai-Schweiger, Markus Schwaiger
We present the first results of the MINDVIEW project. An innovative imaging system for the human brain examination, allowing simultaneous acquisition of PET/MRI images, has been designed and constructed. It consists of a high sensitivity and high resolution PET scanner integrated in a novel, head-dedicated, radio frequency coil for a 3T MRI scanner. Preliminary measurements from the PET scanner show sensitivity 3 times higher than state-of-the-art PET systems that will allow safe repeated studies on the same patient...
February 1, 2018: European Psychiatry: the Journal of the Association of European Psychiatrists
H Cardoso-Cruz, M Dourado, C Monteiro, V Galhardo
BACKGROUND: Dopamine (DA) is thought to be important to local hippocampal networks integrity during spatial working memory (sWM) processing. Chronic pain may contribute to deficient dopaminergic signalling, which may in turn affect cognition. However, the neural mechanisms that determine this impairment are poorly understood. Here, we evaluated whether the sWM impairment characteristic of animal models of chronic pain is dependent on DA D2 receptor (D2r) activity. METHODS: To address this issue, we implanted multichannel arrays of electrodes in the dorsal and ventral hippocampal CA1 field (dvCA1) of rats and recorded the neuronal activity during a classical delayed food-reinforced T-maze sWM task...
January 26, 2018: European Journal of Pain: EJP
Ike C Dela Peña, Guofang Shen, Wei-Xing Shi
Amphetamine-like psychostimulants, including methylphenidate, have been shown to produce two opposing effects on dopamine (DA) neurons: a DA receptor-mediated feedback inhibition and a non-DA receptor-mediated excitation. To test whether the latter effect is mediated through the prefrontal cortex (PFC), we made dual-site recordings from the PFC and ventral tegmental area (VTA). Consistent with previous reports, methylphenidate inhibited VTA DA neurons. The D2 receptor antagonist raclopride completely reversed the inhibition and further increased the activity, particularly bursting, to above pre-drug baseline...
January 12, 2018: Neuropharmacology
Lauri Nummenmaa, Lauri Tuominen, Jussi Hirvonen
Positron emission tomography (PET) and endogenous competition paradigms are widely used for studying neuroreceptor activation in humans in vivo. Changes in cerebral blood triggered by the experimentation, such as amphetamine administration, could influence both tracer delivery and washout, thus biasing the results. A recent study tested this assumption in baboons by measuring radiotracer binding with PET while measuring simultaneously cerebral blood flow with arterial spin labeled functional magnetic resonance imaging...
January 5, 2018: ACS Chemical Neuroscience
Sandeep S V Golla, Sofie M Adriaanse, Maqsood Yaqub, Albert D Windhorst, Adriaan A Lammertsma, Bart N M van Berckel, Ronald Boellaard
BACKGROUND:  Several criteria exist to identify the optimal model for quantification of tracer kinetics. The purpose of this study was to evaluate the correspondence in kinetic model preference identification for brain PET studies among five model selection criteria: Akaike Information Criterion (AIC), AIC unbiased (AICC ), model selection criterion (MSC), Schwartz Criterion (SC), and F-test. MATERIALS AND METHODS: Six tracers were evaluated: [11 C]FMZ, [11 C]GMOM, [11 C]PK11195, [11 C]Raclopride, [18 F]FDG, and [11 C]PHT, including data from five subjects per tracer...
December 6, 2017: EJNMMI Physics
William S John, Thomas J Martin, Kiran Kumar Solingapuram Sai, Susan H Nader, H Donald Gage, Akiva Mintz, Michael A Nader
Cannabis-related impairments to cognitive function may represent novel therapeutic targets for cannabis-use disorder, although the nature, persistence, and reversibility of such deficits remain unclear. Adult male rhesus monkeys ( N = 6) responded in the morning on tasks designed to assess different cognitive domains using the Cambridge Neuropsychological Test Automated Battery (CANTAB) touchscreens followed by responding maintained under a fixed-ratio (FR) 10 schedule of food presentation in different operant chambers...
February 2018: Journal of Pharmacology and Experimental Therapeutics
Fumihiro Saika, Norikazu Kiguchi, Naoki Wakida, Daichi Kobayashi, Yohji Fukazawa, Shinsuke Matsuzaki, Shiroh Kishioka
We previously showed that the CC-chemokine ligand 2 (CCL2)-CC-chemokine receptor 2 (CCR2) system is responsible for conditioned place preference (CPP) by methamphetamine (Meth). In this study, we investigated the roles for other chemokines mediating Meth-induced CPP and the upstream factors upregulating chemokines in mice. We found that CCL7 mRNA level was upregulated in the prefrontal cortex (PFC) after Meth administration (3mg/kg, subcutaneous), and increased CCL7 immunoreactivity was localized to the PFC NeuN-positive neurons...
February 5, 2018: Neuroscience Letters
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
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
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
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
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
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
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
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
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
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