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https://www.readbyqxmd.com/read/28431630/kynurenic-acid-and-its-analogue-can-alter-the-opioid-receptor-g-protein-signaling-after-acute-treatment-via-nmda-receptor-in-rat-cortex-and-striatum
#1
Reza Samavati, Ferenc Zádor, Edina Szűcs, Bernadett Tuka, Diána Martos, Gábor Veres, Róbert Gáspár, István M Mándity, Ferenc Fülöp, László Vécsei, Sándor Benyhe, Anna Borsodi
Previously, we have shown that the N-methyl d-aspartate (NMDA)-receptor antagonist kynurenic acid (KYNA) and its analogue KYNA1 do not bind directly to mu, kappa and delta opioid receptors in vitro. On the other hand, chronic administration of KYNA and KYNA1 resulted in region (cortex vs striatum) and opioid receptor-type specific alterations in G-protein activation of mouse brain homogenates. Here we describe for the first time the acute effect of KYNA and KYNA1 on opioid receptor function with the possible involvement of the NMDA receptor...
May 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28429311/improving-animal-welfare-using-continuous-nalbuphine-infusion-in-a-long-term-rat-model-of-sepsis
#2
Victor Jeger, Mattia Arrigo, Florian F Hildenbrand, Daniel Müller, Paulin Jirkof, Till Hauffe, Burkhardt Seifert, Margarete Arras, Donat R Spahn, Dominique Bettex, Alain Rudiger
BACKGROUND: Sepsis research relies on animal models to investigate the mechanisms of the dysregulated host response to infection. Animal welfare concerns request the use of potent analgesics for the Refinement of existing sepsis models, according to the 3Rs principle. Nevertheless, adequate analgesia is often missing, partly because the effects of analgesics in this particular condition are unknown. We evaluated the use of nalbuphine, an opioid with kappa agonistic and mu antagonistic effects, in rats with and without experimental sepsis...
December 2017: Intensive Care Medicine Experimental
https://www.readbyqxmd.com/read/28412878/-top-down-mu-opioid-system-function-in-humans-mu-opioid-receptors-in-ventrolateral-prefrontal-cortex-mediate-the-relationship-between-hedonic-tone-and-executive-function-in-major-depressive-disorder
#3
Sharee N Light, Linas A Bieliauskas, Jon-Kar Zubieta
Cognitive dysfunction and anhedonia, the reduced ability to experience pleasure, are commonly comorbid symptoms that are persistent following successful resolution of negative affect in major depressive disorder (MDD). Little is known about whether they share common etiology. In the present study, the relationship between ventrolateral prefrontal cortex (VLPFC) activity, cognitive dysfunction (i.e., executive dysfunction), and positive emotionality was investigated in conjunction with mu-opioid neurotransmission in a sample of 39 MDD patients...
April 17, 2017: Journal of Neuropsychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/28411124/m3-muscarinic-acetylcholine-receptor-facilitates-the-endocytosis-of-mu-opioid-receptor-mediated-by-morphine-independently-of-the-formation-of-heteromeric-complexes
#4
Juan F Lopez-Gimenez, Elisa Alvarez-Curto, Graeme Milligan
Morphine inefficiency to induce the internalization of mu opioid (MOP) receptors observed in numerous experimental models constitutes a paradigm of G-protein coupled receptor (GPCR) functional selectivity. We recently described that activation of Gαq/11 proteins through 5-HT2A serotonin receptors co-expressed in the same cells facilitates MOP receptor endocytosis promoted by morphine. In order to explore whether a different Gαq/11 coupled GPCR would emulate this effect, a double stable Flp-In T-REx HEK293 cell line permanently expressing MOP-YFP receptors along with FLAG-M3-Cerulean receptors expressed in an inducible manner was generated...
April 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28407740/mu-opioid-receptor-and-delta-opioid-receptor-differentially-regulate-microglial-inflammatory-response-to-control-proopiomelanocortin-neuronal-apoptosis-in-the-hypothalamus-effects-of-neonatal-alcohol
#5
Pallavi Shrivastava, Miguel A Cabrera, Lucy G Chastain, Nadka I Boyadjieva, Shaima Jabbar, Tina Franklin, Dipak K Sarkar
BACKGROUND: Opioid receptors are known to control neurotransmission of various peptidergic neurons, but their potential role in regulation of microglia and neuronal cell communications is unknown. We investigated the role of mu-opioid receptors (MOR) and delta-opioid receptors (DOR) on microglia in the regulation of apoptosis in proopiomelanocortin (POMC) neurons induced by neonatal ethanol in the hypothalamus. METHODS: Neonatal rat pups were fed a milk formula containing ethanol or control diets between postnatal days 2-6...
April 14, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28394447/mu-opioid-receptor-signaling-in-the-nucleus-accumbens-shell-increases-responsiveness-of-satiety-modulated-lateral-hypothalamus-neurons
#6
Shashank Tandon, Kristen A Keefe, Sharif A Taha
Opioid signaling in the nucleus accumbens shell (sNAcc) has been implicated in hedonic feeding and binge-eating behavior. The sNAcc projects to the lateral hypothalamus (LH), and this pathway has been suggested to modulate palatability-driven feeding behavior. In this study, we investigated the effects of sNAcc mu opioid receptor stimulation on firing rates of LH neurons in previously sated rats. Neural firing in the LH was recorded while food-deprived rats performed an operant task to obtain sweetened Intralipid (a 4% fat emulsion containing 5% sucrose) before and after bilateral sNAcc infusion of either a mu opioid receptor (MOR) agonist, [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO), or a saline control solution...
April 10, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28392713/a-case-report-on-the-treatment-of-complex-chronic-pain-and-opioid-dependence-by-a-multidisciplinary-transitional-pain-service-using-the-act-matrix-and-buprenorphine-naloxone
#7
Aliza Z Weinrib, Lindsay C Burns, Alex Mu, Muhammad Abid Azam, Salima Sj Ladak, Karen McRae, Rita Katznelson, Saam Azargive, Cieran Tran, Joel Katz, Hance Clarke
In an era of growing concern about opioid prescribing, the postsurgical period remains a critical window with the risk of significant opioid dose escalation, particularly in patients with a history of chronic pain and presurgical opioid use. The purpose of this case report is to describe the multidisciplinary care of a complex, postsurgical pain patient by an innovative transitional pain service (TPS). A 59-year-old male with complex chronic pain, as well as escalating long-term opioid use, presented with a bleeding duodenal ulcer requiring emergency surgery...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28391071/non-medical-opioid-use-in-youth-gender-differences-in-risk-factors-and-prevalence
#8
Vicki Osborne, Mirsada Serdarevic, Hannah Crooke, Catherine Striley, Linda B Cottler
BACKGROUND: Non-medical use (NMU) of prescription opioids in youth is of concern since they may continue this pattern into adulthood and become addicted or divert medications to others. Research into risk factors for NMU can help target interventions to prevent non-medical use of opioids in youth. METHOD: The National Monitoring of Adolescent Prescription Stimulants Study (N-MAPSS) was conducted from 2008 to 2011. Participants 10-18years of age were recruited from entertainment venues in urban, rural and suburban areas of 10 US cities...
March 31, 2017: Addictive Behaviors
https://www.readbyqxmd.com/read/28381559/identification-of-a-signaling-cascade-that-maintains-constitutive-delta-opioid-receptor-incompetence-in-peripheral-sensory-neurons
#9
Allison Doyle Brackley, Shayda Sarrami, Ruben Gomez, Kristi A Guerrero, Nathaniel A Jeske
Mu opioid receptor (MOR) agonists are often used to treat severe pain, but can result in adverse side effects. To circumvent systemic side effects, targeting peripheral opioid receptors is an attractive alternative treatment for severe pain. Activation of the delta opioid receptor (DOR) produces similar analgesia with reduced side effects. However, until primed by inflammation, peripheral DOR is analgesically incompetent, raising interest in the mechanism. We recently identified a novel role for G protein-coupled receptor kinase 2 (GRK2) that renders DOR analgesically incompetent at the plasma membrane...
April 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28380057/specific-behavioral-and-cellular-adaptations-induced-by-chronic-morphine-are-reduced-by-dietary-omega-3-polyunsaturated-fatty-acids
#10
Joshua Hakimian, Ani Minasyan, Lily Zhe-Ying, Mariana Loureiro, Austin Beltrand, Camille Johnston, Alexander Vorperian, Nicole Romaneschi, Waleed Atallah, Fernando Gomez-Pinilla, Wendy Walwyn
Opiates, one of the oldest known drugs, are the benchmark for treating pain. Regular opioid exposure also induces euphoria making these compounds addictive and often misused, as shown by the current epidemic of opioid abuse and overdose mortalities. In addition to the effect of opioids on their cognate receptors and signaling cascades, these compounds also induce multiple adaptations at cellular and behavioral levels. As omega-3 polyunsaturated fatty acids (n-3 PUFAs) play a ubiquitous role in behavioral and cellular processes, we proposed that supplemental n-3 PUFAs, enriched in docosahexanoic acid (DHA), could offset these adaptations following chronic opioid exposure...
2017: PloS One
https://www.readbyqxmd.com/read/28376280/independent-and-interactive-effects-of-oprm1-and-dat1-polymorphisms-on-alcohol-consumption-and-subjective-responses-in-social-drinkers
#11
Elise M Weerts, Gary S Wand, Brion Maher, Xiaoqiang Xu, Mary Ann Stephens, Xiaoju Yang, Mary E McCaul
BACKGROUND: The current study examined independent and interactive effects of polymorphisms of the mu opioid receptor gene (OPRM1, A118G) and variable number tandem repeats of the dopamine transporter gene (DAT1, SLC6A3) on alcohol consumption and subjective responses to alcohol in 127 young, healthy, social drinkers. METHODS: Participants completed an in-person assessment, which included self-reported alcohol drinking patterns and blood sampling for DNA, and in a second visit, a cumulative alcohol dosing procedure with subjective ratings across multiple time points and breath alcohol concentrations (0...
April 4, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28374069/mu-and-kappa-opioid-receptors-of-the-periaqueductal-gray-stimulate-and-inhibit-thermogenesis-respectively-during-psychological-stress-in-rats
#12
Caroline Cristina-Silva, Victor Martins, Luciane H Gargaglioni, Kênia C Bícego
The periaqueductal gray matter (PAG) is rich in mu and kappa opioid receptors, and this system is involved in thermoregulation, analgesia, and defensive behaviors. No study approached the involvement of the PAG opioids in body temperature (Tb) regulation during psychological stress such as restraint. Because activation of mu and kappa receptors increases and reduces Tb, respectively, we tested the hypothesis that they exert excitatory and inhibitory modulation, respectively, of the restraint-induced fever in rats...
April 4, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28369738/mu-opioid-receptor-social-behaviour-and-autism-spectrum-disorder-reward-matters
#13
REVIEW
Lucie P Pellissier, Jorge Gandia, Thibaut Laboute, Jerome Aj Becker, Julie Le Merrer
The endogenous opioid system is well known to relieve pain and underpin the rewarding properties of most drugs of abuse. Among opioid receptors, the μ opioid receptor (μOR) mediates most of the analgesic and rewarding properties of opioids. Based on striking similarities between social distress, physical pain and opiate withdrawal, μOR has been proposed to play a critical role in modulating social behaviour in humans and animals. This review summarizes experimental data demonstrating such role and proposes a novel model, the μOR Balance Model, to account for μOR contribution to the subtle regulation of social behaviour...
April 3, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28364251/allosteric-modulation-model-of-the-mu-opioid-receptor-by-herkinorin-a-potent-not-alkaloidal-agonist
#14
A F Marmolejo-Valencia, K Martínez-Mayorga
Modulation of opioid receptors is the primary choice for pain management and structural information studies have gained new horizons with the recently available X-ray crystal structures. Herkinorin is one of the most remarkable salvinorin A derivative with high affinity for the mu opioid receptor, moderate selectivity and lack of nitrogen atoms on its structure. Surprisingly, binding models for herkinorin are lacking. In this work, we explore binding models of herkinorin using automated docking, molecular dynamics simulations, free energy calculations and available experimental information...
March 31, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28361126/pressure-sensitivity-and-phenotypic-changes-in-patients-with-suspected-opioid-induced-hyperalgesia-being-withdrawn-from-full-mu-agonists
#15
Ronald A Wasserman, Afton L Hassett, Steven E Harte, Jenna Goesling, Herbert L Malinoff, Daniel W Berland, Jennifer Zollars, Stephanie E Moser, Chad M Brummett
OBJECTIVES: To assess changes in phenotype and pressure sensitivity in patients with suspected opioid-induced-hyperalgesia (OIH) after transitioning to buprenorphine. METHODS: Twenty patients with suspected OIH were enrolled to transition to buprenorphine therapy. Patients completed validated self-report measures at baseline and at 1, 4, 8 weeks, and 6 months after initiation of buprenorphine along with quantitative sensory testing including measures of pressure pain threshold, pain tolerance and Pain 50 (a pain intensity rating)...
February 2017: Journal of Nature and Science
https://www.readbyqxmd.com/read/28350844/isolation-and-characterization-of-alternatively-spliced-variants-of-the-mouse-sigma1-receptor-gene-sigmar1
#16
Ling Pan, David A Pasternak, Jin Xu, Mingming Xu, Zhigang Lu, Gavril W Pasternak, Ying-Xian Pan
The sigma1 receptor acts as a chaperone at the endoplasmic reticulum, associates with multiple proteins in various cellular systems, and involves in a number of diseases, such as addiction, pain, cancer and psychiatric disorders. The sigma1 receptor is encoded by the single copy SIGMAR1 gene. The current study identifies five alternatively spliced variants of the mouse sigma1 receptor gene using a polymerase chain reaction cloning approach. All the splice variants are generated by exon skipping or alternative 3' or 5' splicing, producing the truncated sigma1 receptor...
2017: PloS One
https://www.readbyqxmd.com/read/28349993/cannabinoid-receptor-type-1-and-mu-opioid-receptor-polymorphisms-are-associated-with-cyclic-vomiting-syndrome
#17
Andrzej Wasilewski, Urszula Lewandowska, Paula Mosinska, Cezary Watala, Martin Storr, Jakub Fichna, Thangam Venkatesan
OBJECTIVES: Cyclic vomiting syndrome (CVS) is a disorder defined by recurrent, unexplained episodes of severe nausea and vomiting. Our aim was to investigate whether CVS and pathophysiological mechanisms underlying this condition are associated with selected variations in genes encoding the components of the endogenous cannabinoid and opioid systems. METHODS: This case-control study included 65 patients with CVS-16 male and 49 female, and 1,092 healthy controls-525 male and 567 female from the 1000 Genomes Project...
March 28, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28343361/genetic-dissociation-of-morphine-analgesia-from-hyperalgesia-in-mice
#18
Gina F Marrone, Valerie Le Rouzic, Andras Varadi, Jin Xu, Anjali M Rajadhyaksha, Susruta Majumdar, Ying-Xian Pan, Gavril W Pasternak
RATIONALE: Morphine is the prototypic mu opioid, producing its analgesic actions through traditional 7 transmembrane domain (7TM) G-protein-coupled receptors generated by the mu opioid receptor gene (Oprm1). However, the Oprm1 gene undergoes extensive alternative splicing to yield three structurally distinct sets of splice variants. In addition to the full-length 7TM receptors, it produces a set of truncated variants comprised of only 6 transmembrane domains (6TM). OBJECTIVES: This study explored the relative contributions of 7TM and 6TM variants in a range of morphine actions...
March 25, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28341892/aquaporin-4-forms-a-macromolecular-complex-with-glutamate-transporter-1-and-mu-opioid-receptor-in-astrocytes-and-participates-in-morphine-dependence
#19
Hui Wang, Shiqi Wang, Kang Zhang, Hua Wang, Liting Lan, Xiaoyun Ma, Xiaoyan Liu, Shuzhuo Zhang, Jianquan Zheng, Xiaoli Wei, Haitao Yan
The water channel aquaporin 4 (AQP4) is abundantly expressed in astrocytes and provides a mechanism by which water permeability of the plasma membrane can be regulated. Evidence suggests that AQP4 is associated with glutamate transporter-1 (GLT-1) for glutamate clearance and contributes to morphine dependence. Previous studies show that AQP4 deficiency changed the mu opioid receptor expression and opioid receptors' characteristics as well. In this study, we focused on whether AQP4 could form macromolecular complex with GLT-1 and mu opioid receptor (MOR) and participates in morphine dependence...
March 24, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28340145/human-abuse-potential-of-the-new-opioid-analgesic-molecule-nktr-181-compared-with-oxycodone
#20
Lynn Webster, Jack Henningfield, August R Buchhalter, Suresh Siddhanti, Lin Lu, Aleksandrs Odinecs, Carlo J Di Fonzo, Michael A Eldon
Objective.:  Evaluate the human abuse potential, pharmacokinetics, pharmacodynamics, and safety of NKTR-181, a novel mu-opioid agonist molecule, relative to oxycodone. Design.:  This randomized, single-center, double-blind, active- and placebo-controlled five-period crossover study enrolled healthy, adult, non-physically dependent recreational opioid users. Setting.:  Inpatient clinical research site. Subjects. : Forty-two randomized subjects (73...
March 10, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
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