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Dopamine and effort

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https://www.readbyqxmd.com/read/28593190/nucleus-accumbens-shell-dopamine-preferentially-tracks-information-related-to-outcome-value-of-reward
#1
Deirdre A Sackett, Michael P Saddoris, Regina M Carelli
Effective decision-making requires organisms to predict reward values and bias behavior toward the best available option. The mesolimbic dopamine system, including the nucleus accumbens (NAc) shell and core, is involved in this process. Although studies support a role of the shell and core in specific aspects of decision-making (e.g., risk, effort, delay), no studies have directly compared dopamine release dynamics in these subregions to cues exclusively signaling the availability of different reward magnitudes...
May 2017: ENeuro
https://www.readbyqxmd.com/read/28555096/role-of-anterior-cingulate-cortex-in-instrumental-learning-blockade-of-dopamine-d1-receptors-suppresses-overt-but-not-covert-learning
#2
Mayada Aly-Mahmoud, Pascal Carlier, Sherine A Salam, Mariam Houari Selmani, Marie Z Moftah, Monique Esclapez, Driss Boussaoud
HIGHLIGHTS Blockade of dopamine D1 receptors in ACC suppressed instrumental learning when overt responding was required.Covert learning through observation was not impaired.After treatment with a dopamine antagonist, instrumental learning recovered but not the rat's pretreatment level of effort tolerance.ACC dopamine is not necessary for acquisition of task-relevant cues during learning, but regulates energy expenditure and effort based decision. Dopamine activity in anterior cingulate cortex (ACC) is essential for various aspects of instrumental behavior, including learning and effort based decision making...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28552230/strategies-for-bringing-stem-cell-derived-dopamine-neurons-to-the-clinic-the-kyoto-trial
#3
Jun Takahashi
Concerted efforts are realizing cell-based therapy for Parkinson's disease (PD). In this chapter, I describe efforts at the Center for iPS Cell Research and Application (CiRA), Kyoto University. These efforts use induced pluripotent stem cells (iPSCs) as donor cells. The iPSCs were established as human leukocyte antigen homozygous at CiRA and are intended for allogeneic transplantation. Our manufacturing protocol includes a feeder-free cell culture with laminin fragment LM511-E8 and the sorting of CORIN(+) cells...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/28552228/strategies-for-bringing-stem-cell-derived-dopamine-neurons-to-the-clinic-a-european-approach-stem-pd
#4
Agnete Kirkeby, Malin Parmar, Roger A Barker
The treatment of Parkinson's disease (PD) has for over 50 years relied on dopaminergic therapies that are highly effective especially in the early years of the condition, but ultimately are limited by the development of side effects that relate to the nonphysiological stimulation of dopamine receptors including in nonstriatal areas. Targeted regenerative therapies designed to restore specifically the lost dopaminergic innervation of the striatum would therefore represent a major advance in treating PD. Transplantation of human fetal ventral midbrain tissue to the striatum of PD patients has provided proof-of-principle that such an approach can provide long-term clinical benefits with a reduced dependency on any oral dopaminergic agents...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/28539420/a-selective-role-for-dopamine-in-learning-to-maximize-reward-but-not-to-minimize-effort-evidence-from-patients-with-parkinson-s-disease
#5
Vasilisa Skvortsova, Bertrand Degos, Marie-Laure Welter, Marie Vidailhet, Mathias Pessiglione
Instrumental learning is a fundamental process through which agents optimize their choices, taking into account various dimensions of available options, such as the possible reward or punishment outcomes, and the costs associated with potential actions. While the implication of dopamine in learning from choice outcomes is well established, less is known about its role in learning the action costs such as effort. Here, we tested the ability of patients with Parkinson's disease (PD) to maximize monetary rewards and minimize physical efforts in a probabilistic instrumental learning task...
May 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28521704/dopamine-d2-receptors-dimers-how-can-we-pharmacologically-target-them
#6
Marco Carli, Shivakumar Kolachalam, Stefano Aringhieri, Mario Rossi, Luca Giovannini, Roberto Maggio, Marco Scarselli
Dopamine D2 and D3 receptors are important pharmacological targets in Schizophrenia and Parkinson’s disease. Intriguingly, many studies have shown that they form homo- and heterodimers, and they can be targeted in specific tissues with new drugs. In this direction, many efforts have been made to develop new molecules that are able to interact with these receptor dimeric complexes. Among various strategies for targeting dopamine receptors dimers, two distinct classes of compounds, such as bivalent and bitopic ligands, have gained particular attention and their use in pharmacology looks promising...
May 18, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28511252/diagnosis-and-management-of-parkinson-s-disease
#7
Arjun Tarakad, Joseph Jankovic
Despite numerous efforts to identify specific and sensitive biomarkers, the diagnosis of Parkinson's disease (PD) is still based on clinical criteria that include the presence of a combination of cardinal motor features (tremor, rigidity, bradykinesia, and postural instability), other motor features (including freezing of gait and abnormal postures), and numerous nonmotor features. In addition, the presence of atypical features may suggest an alternative diagnosis. Levodopa therapy remains the gold standard in the management of motor features of PD...
April 2017: Seminars in Neurology
https://www.readbyqxmd.com/read/28482609/combining-nt3-overexpressing-mscs-and-plga-microcarriers-for-brain-tissue-engineering-a-potential-tool-for-treatment-of-parkinson-s-disease
#8
Hanieh Moradian, Hamid Keshvari, Hamidreza Fasehee, Rassoul Dinarvand, Shahab Faghihi
Parkinson's disease (PD) is a progressive neurodegenerative disorder that characterized by destruction of substantia nigrostriatal pathway due to the loss of dopaminergic (DA) neurons. Regardless of substantial efforts for treatment of PD in recent years, an effective therapeutic strategy is still missing. In a multidisciplinary approach, bone marrow derived mesenchymal stem cells (BMSCs) are genetically engineered to overexpress neurotrophin-3 (nt-3 gene) that protect central nervous system tissues and stimulates neuronal-like differentiation of BMSCs...
July 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28421658/transcriptional-signatures-of-connectomic-subregions-of-the-human-striatum
#9
Linden Parkes, Ben Fulcher, Murat Yücel, Alex Fornito
Functionally distinct regions of the brain are thought to possess a characteristic connectional fingerprint - a profile of incoming and outgoing connections that defines the function of that area. This observation has motivated efforts to subdivide brain areas using their connectivity patterns. However, it remains unclear whether these connectomically-defined subregions can be distinguished at the molecular level. Here, we combine high-resolution diffusion-weighted magnetic resonance imaging with transcriptomic data to show that connectomically-defined subregions of the striatum carry distinct transcriptional signatures...
April 19, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28373651/fatigue-modulates-dopamine-availability-and-promotes-flexible-choice-reversals-during-decision-making
#10
Pierpaolo Iodice, Claudio Ferrante, Luigi Brunetti, Simona Cabib, Feliciano Protasi, Mark E Walton, Giovanni Pezzulo
During decisions, animals balance goal achievement and effort management. Despite physical exercise and fatigue significantly affecting the levels of effort that an animal exerts to obtain a reward, their role in effort-based choice and the underlying neurochemistry are incompletely known. In particular, it is unclear whether fatigue influences decision (cost-benefit) strategies flexibly or only post-decision action execution and learning. To answer this question, we trained mice on a T-maze task in which they chose between a high-cost, high-reward arm (HR), which included a barrier, and a low-cost, low-reward arm (LR), with no barrier...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28350890/quantification-of-motor-network-dynamics-in-parkinson-s-disease-by-means-of-landscape-and-flux-theory
#11
Han Yan, Jin Wang
The basal ganglia neural circuit plays an important role in motor control. Despite the significant efforts, the understanding of the principles and underlying mechanisms of this modulatory circuit and the emergence of abnormal synchronized oscillations in movement disorders is still challenging. Dopamine loss has been proved to be responsible for Parkinson's disease. We quantitatively described the dynamics of the basal ganglia-thalamo-cortical circuit in Parkinson's disease in terms of the emergence of both abnormal firing rates and firing patterns in the circuit...
2017: PloS One
https://www.readbyqxmd.com/read/28334444/the-partial-dopamine-d2-receptor-agonist-aripiprazole-is-associated-with-weight-gain-in-adolescent-anorexia-nervosa
#12
Guido K W Frank, Megan E Shott, Jennifer O Hagman, Marissa A Schiel, Marisa C DeGuzman, Brogan Rossi
OBJECTIVE: Finding medication to support treatment of anorexia nervosa has been difficult. Neuroscience-based approaches may help in this effort. Recent brain imaging studies in adults and adolescents with anorexia nervosa suggest that dopamine-related reward circuits are hypersensitive and could provide a treatment target. METHODS: Here, we present a retrospective chart review of 106 adolescents with anorexia nervosa some of whom were treated with the dopamine D2 receptor partial agonist aripiprazole during treatment in a specialized eating disorder program...
April 2017: International Journal of Eating Disorders
https://www.readbyqxmd.com/read/28326032/a-dynamic-circuit-hypothesis-for-the-pathogenesis-of-blepharospasm
#13
David A Peterson, Terrence J Sejnowski
Blepharospasm (sometimes called "benign essential blepharospasm," BEB) is one of the most common focal dystonias. It involves involuntary eyelid spasms, eye closure, and increased blinking. Despite the success of botulinum toxin injections and, in some cases, pharmacologic or surgical interventions, BEB treatments are not completely efficacious and only symptomatic. We could develop principled strategies for preventing and reversing the disease if we knew the pathogenesis of primary BEB. The objective of this study was to develop a conceptual framework and dynamic circuit hypothesis for the pathogenesis of BEB...
2017: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/28294055/therapeutic-molecular-and-computational-aspects-of-novel-monoamine-oxidase-mao-inhibitors
#14
M Ramesh, Yussif M Dokurugu, Michael D Thompson, Mahmoud Soliman
Due to the limited number of MAOs inhibitors in the clinic and several research efforts are aimed at the discovery of novel MAOs inhibitors. At present, high specificity and a reversible mode of inhibition of MAO-A/B are cited as desirable traits in drug discovery process. This will help to reduce the probability of causing target disruption and may increase the duration of action. Most of the existing MAO inhibitors lead to side effects due to lack of affinity and selectivity. Therefore, there is an urgent need to design novel, potent, reversible and selective inhibitors for MAO-A/B...
March 10, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28283562/effort-based-reinforcement-processing-and-functional-connectivity-underlying-amotivation-in-medicated-patients-with-depression-and-schizophrenia
#15
Il Ho Park, Boung Chul Lee, Jae-Jin Kim, Joong Il Kim, Min-Seung Koo
Amotivation is a common phenotype of major depressive disorder and schizophrenia, which are clinically distinct disorders. Effective treatment targets and strategies can be discovered by examining the dopaminergic reward network function underlying amotivation between these disorders. We conducted an fMRI study in healthy human participants and medicated patients with depression and schizophrenia using an effort-based reinforcement task. We examined regional activations related to reward type (positive and negative reinforcement), effort level, and their composite value, as well as resting-state functional connectivities within the meso-striatal-prefrontal pathway...
April 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28282811/replacing-dopamine-neurons-in%C3%A2-parkinson-s-disease-how-did-it-happen
#16
Anders Björklund, Olle Lindvall
The efforts to develop a dopamine cell replacement therapy for Parkinson's disease have spanned over more than three decades. Based on almost 10 years of transplantation studies in animal models, the first patients receiving grafts of fetal-derived dopamine neuroblasts were operated in Lund in 1987. Over the following two decades, a total of 18 patients were transplanted and followed closely by our team with mixed but also very encouraging results. In this article we tell the story of how the preclinical and clinical transplantation program in Lund evolved...
2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28265019/the-first-negative-allosteric-modulator-for-dopamine-d2-and-d3-receptors-sb269652-may-lead-to-a-new-generation-of-antipsychotic-drugs
#17
REVIEW
Mario Rossi, Irene Fasciani, Francesco Marampon, Roberto Maggio, Marco Scarselli
D2 and D3 dopamine receptors belong to the largest family of cell surface proteins in eukaryotes, the G protein-coupled receptors (GPCRs). Considering their crucial physiologic functions and their relatively accessible cellular locations, GPCRs represent one of the most important classes of therapeutic targets. Until recently, the only strategy to develop drugs regulating GPCR activity was through the identification of compounds that directly acted on the orthosteric sites for endogenous ligands. However, many efforts have recently been made to identify small molecules that are able to interact with allosteric sites...
June 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28261071/trial-by-trial-modulation-of-associative-memory-formation-by-reward-prediction-error-and-reward-anticipation-as-revealed-by-a-biologically-plausible-computational-model
#18
Kristoffer C Aberg, Julia Müller, Sophie Schwartz
Anticipation and delivery of rewards improves memory formation, but little effort has been made to disentangle their respective contributions to memory enhancement. Moreover, it has been suggested that the effects of reward on memory are mediated by dopaminergic influences on hippocampal plasticity. Yet, evidence linking memory improvements to actual reward computations reflected in the activity of the dopaminergic system, i.e., prediction errors and expected values, is scarce and inconclusive. For example, different previous studies reported that the magnitude of prediction errors during a reinforcement learning task was a positive, negative, or non-significant predictor of successfully encoding simultaneously presented images...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28225217/proteomic-analysis-of-the-cullin-4b-interactome-using-proximity-dependent-biotinylation-in-living-cells
#19
Hailong Zhang, Shupeng Li, Pingting Liu, Frankie H F Lee, Albert H C Wong, Fang Liu
Cullin 4B (CUL4B) mutations have been implicated in mental retardation and dopamine-related behaviors due to disruptions in their interaction with cullin-RING E3 ligases (CRLs). Thus, further identification of CUL4B substrates can increase the knowledge of protein homeostasis and illuminate the role of CUL4B in neuropsychiatric disease. However, the transient nature of the coupling between CUL4B and its substrates is difficult to detect in vivo using current approaches, thus hampers efforts to investigate functions of CRLs within unperturbed living systems...
April 2017: Proteomics
https://www.readbyqxmd.com/read/28204862/effect-of-constant-predictable-and-unpredictable-motor-tasks-on-motor-performance-and-blood-markers-of-stress
#20
Laura Kyguoliene, Albertas Skurvydas, Nerijus Eimantas, Neringa Baranauskienė, Dalia Mickeviciene, Daiva Urboniene, Margarita Cernych, Marius Brazaitis
An unfamiliar or novel physical stimulus induces activation of dopaminergic neurons within the brain and greater activity in areas involved in emotion; considering this, we aimed to establish whether unpredictable prolonged (fatiguing) motor task (vs. constant vs. predictable) evokes greater dopaminergic activity, enhances neuromuscular performance, motor accuracy, and perception of effort, and delays overall central fatigue. Fifteen healthy male volunteers (aged 22 ± 4 years) were required to perform 1 of 3 exercise trials (at least 1 week apart) of 100 intermittent isometric contraction (IIC) tasks involving knee extensions at 60° flexion...
February 16, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
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