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https://www.readbyqxmd.com/read/28103011/discovery-of-a-phosphonoacetic-acid-derived-natural-product-by-pathway-refactoring
#1
Todd S Freestone, Kou-San Ju, Bin Wang, Huimin Zhao
The activation of silent natural product gene clusters is a synthetic biology problem of great interest. As the rate at which gene clusters are identified outpaces the discovery rate of new molecules, this unknown chemical space is rapidly growing, as too are the rewards for developing technologies to exploit it. One class of natural products that has been underrepresented is phosphonic acids, which have important medical and agricultural uses. Hundreds of phosphonic acid biosynthetic gene clusters have been identified encoding for unknown molecules...
January 19, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28097729/the-role-of-orexin-signaling-in-the-ventral-tegmental-area-and-central-amygdala-in-modulating-binge-like-ethanol-drinking-behavior
#2
Jeffrey J Olney, Montserrat Navarro, Todd E Thiele
BACKGROUND: Recent reports have demonstrated that binge-like ethanol drinking leads to an increase in hypothalamic orexin (OX) signaling and that suppressing this signaling via systemic administration of an orexin receptor (OXR) antagonist blocks this behavior; however, the specific OX pathways that modulate this behavior remain unknown. The goal of the present study was to further elucidate the role of the OX system in binge-like ethanol drinking using behavioral, molecular, and pharmacological techniques...
January 17, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28093305/role-of-leptin-in-conditioned-place-preference-to-high-fat-diet-in-leptin-deficient-ob-ob-mice
#3
Yoshiyuki Shimizu, Cheol Son, Daisuke Aotani, Hidenari Nomura, Takatoshi Hikida, Kiminori Hosoda, Kazuwa Nakao
Leptin is an adipocyte-derived anorexic hormone that exerts its effects via the hypothalamus and other brain regions, including the reward system. Leptin-deficient ob/ob mice that present morbid obesity, hyperphagia, insulin resistance, and infertility are one of the most investigated mouse models of obesity. Conditioned place preference (CPP) paradigm is a standard behavioral model to evaluate the rewarding value of substrates. While leptin is reported to decrease the CPP of lean mice for high fat diet (HFD), it is unknown how CPP toward HFD is affected by leptin replacement in the pathophysiological condition of ob/ob mice...
January 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28092323/brain-substrates-of-reward-processing-and-the-%C3%AE-opioid-receptor-a-pathway-into-pain
#4
Frauke Nees, Susanne Becker, Sabina Millenet, Tobias Banaschewski, Luise Poustka, Arun Bokde, Uli Bromberg, Christian Büchel, Patricia J Conrod, Sylvane Desrivières, Vincent Frouin, Jürgen Gallinat, Hugh Garavan, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Dimitri Papadopoulos Orfanos, Tomáš Paus, Michael N Smolka, Henrik Walter, Rob Whelan, Gunter Schumann, Herta Flor
The processing of reward and reinforcement learning seems to be important determinants of pain chronicity. However, reward processing is already altered early in life and if this is related to the development of pain symptoms later on is not known. The aim of this study was first to examine whether behavioural and brain-related indicators of reward processing at the age of 14 to 15 years are significant predictors of pain complaints 2 years later, at 16 to 17 years. Second, we investigated the contribution of genetic variations in the opioidergic system, which is linked to the processing of both, reward and pain, to this prediction...
February 2017: Pain
https://www.readbyqxmd.com/read/28087369/multidimensional-assessment-of-impulsivity-in-relation-to-obesity-and-food-addiction
#5
Lauren VanderBroek-Stice, Monika K Stojek, Steven R H Beach, Michelle R vanDellen, James MacKillop
Based on similarities between overconsumption of food and addictive drugs, there is increasing interest in "food addiction," a compulsive eating pattern defined using symptoms parallel to substance use disorders. Impulsivity, a multidimensional construct robustly linked to drug addiction, has been increasingly examined as an obesity determinant, but with mixed findings. This study sought to clarify relations between three major domains of impulsivity (i.e., impulsive personality traits, discounting of delayed rewards, and behavioral inhibition) in both obesity and food addiction...
January 10, 2017: Appetite
https://www.readbyqxmd.com/read/28065827/gastric-bypass-surgery-recruits-a-gut-ppar-%C3%AE-striatal-d1r-pathway-to-reduce-fat-appetite-in-obese-rats
#6
Mohammed K Hankir, Florian Seyfried, Constantin A Hintschich, Thi-Ai Diep, Karen Kleberg, Mathias Kranz, Winnie Deuther-Conrad, Luis A Tellez, Michael Rullmann, Marianne Patt, Jens Teichert, Swen Hesse, Osama Sabri, Peter Brust, Harald S Hansen, Ivan E de Araujo, Ute Krügel, Wiebke K Fenske
Bariatric surgery remains the single most effective long-term treatment modality for morbid obesity, achieved mainly by lowering caloric intake through as yet ill-defined mechanisms. Here we show in rats that Roux-en-Y gastric bypass (RYGB)-like rerouting of ingested fat mobilizes lower small intestine production of the fat-satiety molecule oleoylethanolamide (OEA). This was associated with vagus nerve-driven increases in dorsal striatal dopamine release. We also demonstrate that RYGB upregulates striatal dopamine 1 receptor (D1R) expression specifically under high-fat diet feeding conditions...
January 2, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28053043/habenula-induced-inhibition-of-midbrain-dopamine-neurons-is-diminished-by-lesions-of-the-rostromedial-tegmental-nucleus
#7
P Leon Brown, Heather Palacorolla, Dana Brady, Katelyn Riegger, Greg I Elmer, Paul D Shepard
: Neurons in the lateral habenula (LHb) are transiently activated by aversive events and have been implicated in associative learning. Functional changes associated with tonic and phasic activation of the LHb are often attributed to a corresponding inhibition of midbrain dopamine (DA) neurons. Activation of GABAergic neurons in the rostromedial tegmental nucleus (RMTg), a region that receives dense projections from the LHb and projects strongly to midbrain monoaminergic nuclei, is believed to underlie the transient inhibition of DA neurons attributed to activation of the LHb...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28053028/activation-of-pedunculopontine-glutamate-neurons-is-reinforcing
#8
Ji Hoon Yoo, Vivien Zell, Johnathan Wu, Cindy Punta, Nivedita Ramajayam, Xinyi Shen, Lauren Faget, Varoth Lilascharoen, Byung Kook Lim, Thomas S Hnasko
: Dopamine transmission from midbrain ventral tegmental area (VTA) neurons underlies behavioral processes related to motivation and drug addiction. The pedunculopontine tegmental nucleus (PPTg) is a brainstem nucleus containing glutamate-, acetylcholine-, and GABA-releasing neurons with connections to basal ganglia and limbic brain regions. Here we investigated the role of PPTg glutamate neurons in reinforcement, with an emphasis on their projections to VTA dopamine neurons. We used cell-type-specific anterograde tracing and optogenetic methods to selectively label and manipulate glutamate projections from PPTg neurons in mice...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28045456/redox-potential-as-a-master-variable-controlling-pathways-of-metal-reduction-by-geobacter-sulfurreducens
#9
Caleb E Levar, Colleen L Hoffman, Aubrey J Dunshee, Brandy M Toner, Daniel R Bond
Geobacter sulfurreducens uses at least two different pathways to transport electrons out of the inner membrane quinone pool before reducing acceptors beyond the outer membrane. When growing on electrodes poised at oxidizing potentials, the CbcL-dependent pathway operates at or below redox potentials of -0.10 V vs the standard hydrogen electrode, whereas the ImcH-dependent pathway operates only above this value. Here, we provide evidence that G. sulfurreducens also requires different electron transfer proteins for reduction of a wide range of Fe(III)- and Mn(IV)-(oxyhydr)oxides, and must transition from a high- to low-potential pathway during reduction of commonly studied soluble and insoluble metal electron acceptors...
January 3, 2017: ISME Journal
https://www.readbyqxmd.com/read/28044061/in-silico-identification-and-in-vivo-validation-of-mir-495-as-a-novel-regulator-of-motivation-for-cocaine-that-targets-multiple-addiction-related-networks-in-the-nucleus-accumbens
#10
R M Bastle, R J Oliver, A S Gardiner, N S Pentkowski, F Bolognani, A M Allan, T Chaudhury, M St Peter, N Galles, C Smith, J L Neisewander, N I Perrone-Bizzozero
MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression and are implicated in the etiology of several neuropsychiatric disorders, including substance use disorders (SUDs). Using in silico genome-wide sequence analyses, we identified miR-495 as a miRNA whose predicted targets are significantly enriched in the Knowledgebase for Addiction Related Genes (ARG) database (KARG; http://karg.cbi.pku.edu.cn). This small non-coding RNA is also highly expressed within the nucleus accumbens (NAc), a pivotal brain region underlying reward and motivation...
January 3, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28042038/exposure-to-food-cues-moderates-the-indirect-effect-of-reward-sensitivity-and-external-eating-via-implicit-eating-expectancies
#11
Aimee L Maxwell, Natalie J Loxton, Julie M Hennegan
Previous research has suggested that the expectancy "eating is rewarding" is one pathway driving the relationship between trait reward sensitivity and externally-driven eating. The aim of the current study was to extend previous research by examining the conditions under which the indirect effect of reward sensitivity and external eating via this eating expectancy occurs. Using a conditional indirect effects approach we tested the moderating effect of exposure to food cues (e.g., images) relative to non-food cues on the association between reward sensitivity and external eating, via eating expectancies...
December 29, 2016: Appetite
https://www.readbyqxmd.com/read/28035534/oprd1-genetic-variation-and-human-disease
#12
Richard C Crist, Toni-Kim Clarke
The OPRD1 gene encodes the delta-opioid receptor, which has multiple functions including regulating reward pathways. The gene contains more than 2,000 verified genetic variants but only 2 currently have evidence for specific functions: rs1042114 disrupts maturation of the receptor and rs569356 affects OPRD1 expression. These polymorphisms and others in the gene have been found to be associated with human diseases. The most reproducible data are associations between opioid addiction and three variants in intron 1 (rs2236861, rs2236857, and rs3766951), which have been described in a number of independent populations...
December 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28033474/hypothesizing-that-neuropharmacological-and-neuroimaging-studies-of-glutaminergic-dopaminergic-optimization-complex-kb220z-are-associated-with-dopamine-homeostasis-in-reward-deficiency-syndrome-rds
#13
Kenneth Blum, Marcelo Febo, Lyle Fried, Mona Li, Kristina Dushaj, Eric R Braverman, Thomas McLaughlin, Bruce Steinberg, Rajendra D Badgaiyan
BACKGROUND: There is need for better treatments of addictive behaviors, both substance and non-substance related, termed Reward Deficiency Syndrome (RDS). While the FDA has approved pharmaceuticals under the umbrella term Medication Assisted Treatment (MAT), these drugs are not optimal. OBJECTIVES: It is our contention that these drugs work well in the short-term by blocking dopamine function leading to psychological extinction. However, use of buprenorphine/Naloxone over a long period of time results in unwanted addiction liability, reduced emotional affect, and mood changes including suicidal ideation...
December 29, 2016: Substance Use & Misuse
https://www.readbyqxmd.com/read/28030757/altered-resting-state-functional-connectivity-of-fear-and-reward-circuitry-in-comorbid-ptsd-and-major-depression
#14
Xi Zhu, Liat Helpman, Santiago Papini, Franklin Schneier, John C Markowitz, Page E Van Meter, Martin A Lindquist, Tor D Wager, Yuval Neria
BACKGROUND: Individuals with comorbid posttraumatic stress disorder and major depressive disorder (PTSD-MDD) often exhibit greater functional impairment and poorer treatment response than individuals with PTSD alone. Research has not determined whether PTSD-MDD is associated with different network connectivity abnormalities than PTSD alone. METHODS: We used functional magnetic resonance imaging (fMRI) to measure resting state functional connectivity (rs-FC) patterns of brain regions involved in fear and reward processing in three groups: patients with PTSD-alone (n = 27), PTSD-MDD (n = 21), and trauma-exposed healthy controls (TEHCs, n = 34)...
December 28, 2016: Depression and Anxiety
https://www.readbyqxmd.com/read/28025809/the-human-orexin-hypocretin-receptor-crystal-structures
#15
Jie Yin, Daniel M Rosenbaum
The human orexin/hypocretin receptors (hOX1R and hOX2R) are G protein-coupled receptors (GPCRs) that mediate the diverse functions of the orexin/hypocretin neuropeptides. Orexins/hypocretins produced by neurons in the lateral hypothalamus stimulate their cognate GPCRs in multiple regions of the central nervous system to control sleep and arousal, circadian rhythms, metabolism, reward pathways, and other behaviors. Dysfunction of orexin/hypocretin signaling is associated with human disease, and the receptors are active targets in a number of therapeutic areas...
December 27, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28025089/histone-deacetylase-5-modulates-the-effects-of-social-adversity-in-early-life-on-cocaine-induced-behavior
#16
Alessandro Valzania, Clarissa Catale, Maria Teresa Viscomi, Stefano Puglisi-Allegra, Valeria Carola
Psychostimulants induce stable changes in neural plasticity and behavior in a transcription-dependent manner. Further, stable cellular changes require transcription that is regulated by epigenetic mechanisms that alter chromatin structure, such as histone acetylation. This mechanism is typically catalyzed by enzymes with histone acetyltransferase or histone deacetylase (HDAC) activity. Class IIa HDACs are notable for their high expression in important regions of the brain reward circuitry and their neural activity-dependent shuttling in and out of the cell nucleus...
December 23, 2016: Physiology & Behavior
https://www.readbyqxmd.com/read/28011402/the-impact-of-the-appetite-regulating-orexigenic-peptide-ghrelin-on-alcohol-use-disorders-a-systematic-review-of-preclinical-and-clinical-data
#17
Anne Koopmann, Rilana Schuster, Falk Kiefer
Ghrelin, which is mainly released from the stomach, is the most important orexigenic regulator of food intake, inducing appetite, enhancing adiposity and releasing growth hormone. Besides the hypothalamus, ghrelin receptors (GHS-R1A) are also expressed in the mesolimbic dopaminergic system, which increases the possibility that ghrelin plays an important role in reward regulation for substance use disorders such as alcohol addiction, especially through activating the cholinergic-dopaminergic reward link. In this review we focus on the impact of ghrelin on the development and maintenance of alcohol addiction/dependence, alcohol consumption, alcohol craving and alcohol withdrawal, attempting to integrate preclinical and clinical studies concerning the intriguing relationship between appetite regulation, reward and alcohol addiction...
December 21, 2016: Biological Psychology
https://www.readbyqxmd.com/read/28007490/gut-brain-nutrient-sensing-in-food-reward
#18
Ari Shechter, Gary J Schwartz
For the past several decades, vagal and hormonal gut-brain negative feedback signaling mechanisms that promote satiety and subsequent suppression of food intake have been explored. In addition, a separate positive feedback process termed "appetition," involving postoral signaling from the gut to the brain, has been shown to promote food intake and produce flavor-nutrient preference conditioning. Afferent fibers emerging from the vagus nerve form the main pathway by which information is relayed from the abdominal viscera to the hindbrain and eventually other higher brain regions involved in food intake...
December 20, 2016: Appetite
https://www.readbyqxmd.com/read/28002987/decision-making-under-uncertainty-in-a-spiking-neural-network-model-of-the-basal-ganglia
#19
Charlotte Héricé, Radwa Khalil, Marie Moftah, Thomas Boraud, Martin Guthrie, André Garenne
The mechanisms of decision-making and action selection are generally thought to be under the control of parallel cortico-subcortical loops connecting back to distinct areas of cortex through the basal ganglia and processing motor, cognitive and limbic modalities of decision-making. We have used these properties to develop and extend a connectionist model at a spiking neuron level based on a previous rate model approach. This model is demonstrated on decision-making tasks that have been studied in primates and the electrophysiology interpreted to show that the decision is made in two steps...
December 21, 2016: Journal of Integrative Neuroscience
https://www.readbyqxmd.com/read/28000031/paradoxical-antidepressant-effects-of-alcohol-are-related-to-acid-sphingomyelinase-and-its-control-of-sphingolipid-homeostasis
#20
Christian P Müller, Liubov S Kalinichenko, Jens Tiesel, Matthias Witt, Thomas Stöckl, Eva Sprenger, Jens Fuchser, Janine Beckmann, Marc Praetner, Sabine E Huber, Davide Amato, Christiane Mühle, Christian Büttner, Arif B Ekici, Irena Smaga, Lucyna Pomierny-Chamiolo, Bartosz Pomierny, Malgorzata Filip, Volker Eulenburg, Erich Gulbins, Anbarasu Lourdusamy, Martin Reichel, Johannes Kornhuber
Alcohol is a widely consumed drug that can lead to addiction and severe brain damage. However, alcohol is also used as self-medication for psychiatric problems, such as depression, frequently resulting in depression-alcoholism comorbidity. Here, we identify the first molecular mechanism for alcohol use with the goal to self-medicate and ameliorate the behavioral symptoms of a genetically induced innate depression. An induced over-expression of acid sphingomyelinase (ASM), as was observed in depressed patients, enhanced the consumption of alcohol in a mouse model of depression...
December 20, 2016: Acta Neuropathologica
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