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Dopamine and effort

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https://www.readbyqxmd.com/read/28421658/transcriptional-signatures-of-connectomic-subregions-of-the-human-striatum
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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 physiological 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 in order to identify small molecules that are able to interact with allosteric sites...
March 6, 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
#10
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-cullin4b-interactome-using-proximity-dependent-biotinylation-in-living-cells
#11
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...
February 22, 2017: Proteomics
https://www.readbyqxmd.com/read/28204862/effect-of-constant-predictable-and-unpredictable-motor-tasks-on-motor-performance-and-blood-markers-of-stress
#12
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
https://www.readbyqxmd.com/read/28202664/lrrk2-mouse-models-dissecting-the-behavior-striatal-neurochemistry-and-neurophysiology-of-pd-pathogenesis
#13
REVIEW
Mattia Volta, Heather Melrose
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of familial Parkinson's disease (PD), resembling the sporadic disorder. Intensive effort has been directed toward LRRK2 mouse modeling and investigation, aimed at reproducing the human disease to inform mechanistic studies of pathogenesis and design of neuroprotective therapies. The physiological function of LRRK2 is still under exploration, but a clear role in striatal neurophysiology and animal behavior has emerged. Alterations in LRRK2 impair dopamine (DA) transmission, regulation and signaling, in addition to corticostriatal synaptic plasticity...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28194005/genetic-inhibition-of-neurotransmission-reveals-role-of-glutamatergic-input-to-dopamine-neurons-in-high-effort-behavior
#14
M A Hutchison, X Gu, M F Adrover, M R Lee, T S Hnasko, V A Alvarez, W Lu
Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions...
February 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28177981/high-fat-diet-alters-weight-caloric-intake-and-haloperidol-sensitivity-in-the-context-of-effort-based-responding
#15
Stephen H Robertson, Steven R Boomhower, Erin B Rasmussen
High-fat (HF) diets result in weight gain, hyperphagia, and reduced dopamine D2 signaling; however, these findings have been obtained only under free-feeding conditions. This study tested the extent to which HF diet affects effort-dependent food procurement and the extent to which dopamine signaling is involved. Male Sprague-Dawley rats consumed either a HF (n=20) or a standard-chow (n=20) diet. We assessed the sensitivity to effort-based reinforcement in 10 rats from each group by measuring consumption across a series of fixed-ratio schedules (FR 5-FR 300) under a closed economy and quantified performance using the exponential-demand equation...
February 7, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28161116/a-review-of-the-theoretical-and-biological-understanding-of-the-nocebo-and-placebo-phenomena
#16
REVIEW
Seetal Dodd, Olivia M Dean, João Vian, Michael Berk
PURPOSE: Placebos are commonly used in experimental and patient populations and are known to influence treatment outcomes. The mechanism of action of placebos has been investigated by several researchers. This review investigates the current knowledge regarding the theoretical and biological underpinning of the nocebo and placebo phenomena. METHOD: Literature was searched using PubMed using the following keywords: nocebo, placebo, μ-opioid, dopamine, conditioning, and expectancy...
February 1, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28154545/influence-of-the-slc6a3-dat1-gene-on-multifaceted-measures-of-self-regulation-in-preschool-children
#17
Lina M Cómbita, Pascale Voelker, Alicia Abundis-Gutiérrez, Joan P Pozuelos, M Rosario Rueda
Development of self-regulation, the capacity to voluntarily modulate thoughts, emotions and actions is strongly related to the maturation of the dopamine-mediated executive attention network (EAN). The attention control processes associated with the EAN greatly overlap with efficiency of the executive functions and are correlated with measures of effortful control. Regulation of dopamine levels within the EAN, particularly in the basal ganglia is carried out by the action of dopamine transporters. In humans, the SLC6A3/DAT1 gene carries out the synthesis of the DAT protein...
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/28117839/the-genetic-overlap-between-mood-disorders-and-cardiometabolic-diseases-a-systematic-review-of-genome-wide-and-candidate-gene-studies
#18
REVIEW
A T Amare, K O Schubert, M Klingler-Hoffmann, S Cohen-Woods, B T Baune
Meta-analyses of genome-wide association studies (meta-GWASs) and candidate gene studies have identified genetic variants associated with cardiovascular diseases, metabolic diseases and mood disorders. Although previous efforts were successful for individual disease conditions (single disease), limited information exists on shared genetic risk between these disorders. This article presents a detailed review and analysis of cardiometabolic diseases risk (CMD-R) genes that are also associated with mood disorders...
January 24, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28108196/homovanillic-acid-in-csf-of-mild-stage-parkinson-s-disease-patients-correlates-with-motor-impairment
#19
Alessandro Stefani, Mariangela Pierantozzi, Enrica Olivola, Salvatore Galati, Rocco Cerroni, Vincenza D'Angelo, Atticus H Hainsworth, Valentina Saviozzi, Ernesto Fedele, Claudio Liguori
In Parkinson's disease (PD), several efforts have been spent in order to find biochemical parameters able to identify the progression of the pathological processes at the basis of the disease. It is already known that advanced PD patients manifesting dyskinesia are featured by the high homovanillic acid (HVA)/dopamine (DA) ratio, suggesting the increased turnover of DA in these patients. Less clear is whether similar changes affect mild and moderate stages of the disease (between 1 and 2.5 of Hoehn & Yahr -H&Y- stage)...
May 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28088492/pikuni-blackfeet-traditional-medicine-neuroprotective-activities-of-medicinal-plants-used-to-treat-parkinson-s-disease-related-symptoms
#20
Aurélie de Rus Jacquet, Mitali Arun Tambe, Sin Ying Ma, George P McCabe, Jay Hansford C Vest, Jean-Christophe Rochet
ETHNOPHARMACOLOGICAL RELEVANCE: Parkinson's disease (PD) is a multifactorial neurodegenerative disorder affecting 5% of the population over the age of 85 years. Current treatments primarily involve dopamine replacement therapy, which leads to temporary relief of motor symptoms but fails to slow the underlying neurodegeneration. Thus, there is a need for safe PD therapies with neuroprotective activity. In this study, we analyzed contemporary herbal medicinal practices used by members of the Pikuni-Blackfeet tribe from Western Montana to treat PD-related symptoms, in an effort to identify medicinal plants that are affordable to traditional communities and accessible to larger populations...
January 11, 2017: Journal of Ethnopharmacology
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