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https://www.readbyqxmd.com/read/29341883/title-brain-region-specific-molecular-responses-to-maternal-separation-and-social-defeat-stress-in-mice
#1
Benjamin D Sachs, Ha L Tran, Emily Folse, Marc G Caron
The association between stress and mental illness has been well documented, but the molecular consequences of repeated exposure to stress have not been completely identified. The present study sought to elucidate the combinatorial effects of early life maternal separation stress and adult social defeat stress on alterations in signal transduction and gene expression that have been previously implicated in susceptibility to psychosocial stress. Molecular analyses were performed in the prelimbic/infralimbic cortex, amygdala, and nucleus accumbens, three brain regions that have been suggested to play critical roles in determining stress responses...
January 13, 2018: Neuroscience
https://www.readbyqxmd.com/read/29336871/epigenetic-regulation-of-the-kappa-opioid-receptor-gene-by-an-insertion-deletion-in-the-promoter-region
#2
Pierre-Eric Lutz, Daniel Almeida, Raoul Belzeaux, Ipek Yalcin, Gustavo Turecki
Preclinical and clinical studies have demonstrated that the kappa opioid receptor (KOR) regulates reward, hedonic tone and emotions. At therapeutic level, on-going clinical trials are assessing the potential of targeting the KOR for the management of depression, anxiety disorders and substance use disorders. However, genetic polymorphisms in the KOR gene that potentially contribute to its implication in these phenotypes have been poorly studied. Here we investigated an insertion-deletion in the promoter region of KOR (rs35566036), recently associated with alcohol addiction, in a cohort of depressed subjects who died by suicide, as well as psychiatrically healthy individuals...
January 11, 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29335280/mapping-protein-interactions-of-sodium-channel-nav1-7-using-epitope-tagged-gene-targeted-mice
#3
Alexandros H Kanellopoulos, Jennifer Koenig, Honglei Huang, Martina Pyrski, Queensta Millet, Stéphane Lolignier, Toru Morohashi, Samuel J Gossage, Maude Jay, John E Linley, Georgios Baskozos, Benedikt M Kessler, James J Cox, Annette C Dolphin, Frank Zufall, John N Wood, Jing Zhao
The voltage-gated sodium channel NaV1.7 plays a critical role in pain pathways. We generated an epitope-tagged NaV1.7 mouse that showed normal pain behaviours to identify channel-interacting proteins. Analysis of NaV1.7 complexes affinity-purified under native conditions by mass spectrometry revealed 267 proteins associated with Nav1.7 in vivo The sodium channel β3 (Scn3b), rather than the β1 subunit, complexes with Nav1.7, and we demonstrate an interaction between collapsing-response mediator protein (Crmp2) and Nav1...
January 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29334500/overexpression-of-%C3%A2%C2%B5-opioid-receptors-in-peripheral-afferents-but-not-in-combination-with-enkephalin-decreases-neuropathic-pain-behavior-and-enhances-opioid-analgesia-in-mouse
#4
Amanda H Klein, Husam K Mohammad, Rabiah Ali, Brad Peper, Steven P Wilson, Srinivasa N Raja, Matthias Ringkamp, Sarah Sweitzer
BACKGROUND: The current study used recombinant herpes simplex virus type I to increase expression of µ-opiate receptors and the opioid ligand preproenkephalin in peripheral nerve fibers in a mouse model of neuropathic pain. It was predicted that viral vector delivery of a combination of genes encoding the µ-opioid receptor and preproenkephalin would attenuate neuropathic pain and enhance opioid analgesia. The behavioral effects would be paralleled by changes in response properties of primary afferent neurons...
January 15, 2018: Anesthesiology
https://www.readbyqxmd.com/read/29333880/pharmacogenetic-analysis-of-opioid-dependence-treatment-dose-and-dropout-rate
#5
Richard C Crist, James Li, Glenn A Doyle, Alex Gilbert, Bryan M Dechairo, Wade H Berrettini
BACKGROUND: Currently, no pharmacogenetic tests for selecting an opioid-dependence pharmacotherapy have been approved by the US Food and Drug Administration. OBJECTIVES: Determine the effects of variants in 11 genes on dropout rate and dose in patients receiving methadone or buprenorphine/naloxone (ClinicalTrials.gov Identifier: NCT00315341). METHODS: Variants in six pharmacokinetic genes (CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4) and five pharmacodynamic genes (HTR2A, OPRM1, ADRA2A, COMT, SLC6A4) were genotyped in samples from a 24-week, randomized, open-label trial of methadone and buprenorphine/naloxone for the treatment of opioid dependence (n = 764; 68...
January 15, 2018: American Journal of Drug and Alcohol Abuse
https://www.readbyqxmd.com/read/29330446/effect-of-puerarin-in-promoting-fatty-acid-oxidation-by-increasing-mitochondrial-oxidative-capacity-and-biogenesis-in-skeletal-muscle-in-diabetic-rats
#6
Xiu-Fang Chen, Lei Wang, Yong-Zheng Wu, Shi-Yu Song, Hai-Yan Min, Yan Yang, Xuan He, Qiao Liang, Long Yi, Yong Wang, Qian Gao
BACKGROUND: Type 2 diabetes is characterized by dyslipidemia and the accumulation of lipids in non-adipose tissue, including skeletal muscle. Puerarin, which is a natural isoflavonoid isolated from the root of the plant Pueraria lobata, has been shown to have antidiabetic activity. However, the lipid-reducing effect of puerarin, in particular in skeletal muscle, has not yet been addressed. METHODS: We examined the effect of puerarin on mitochondrial function and the oxidation of fatty acids in the skeletal muscle of high-fat diet/streptozotocin-induced diabetic rats...
January 12, 2018: Nutrition & Diabetes
https://www.readbyqxmd.com/read/29330135/apbb2-is-associated-with-amphetamine-use-and-plasma-beta-amyloids-in-patients-receiving-methadone-maintenance-treatment
#7
Chia-Chen Liu, Chiu-Ping Fang, Tung-Hsia Liu, Hsiang-Wei Kuo, Shu Chi Liu, Sheng-Chang Wang, Andrew C H Chen, Yu-Li Liu
APBB2, amyloid beta (A4) precursor protein-binding family B member 2, has been reported to be associated with opioid dependence. In this study, we reported the first time that the genetic variants in the APBB2 gene were associated with use of amphetamine in opioid dependent patients undergoing methadone maintenance treatment (MMT). 344 heroin-dependent patients undergoing MMT were recruited and assessed for use of amphetamine and opioids by urine toxicology, withdrawal severity, and side effects. DNAs were genome-widely genotyped for all patients...
January 9, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29324390/nfat-1-hyper-activation-by-methionine-enkephalin-menk-significantly-induces-cell-apoptosis-of-rats-c6-glioma-in-vivo-and-in-vitro
#8
Wei-Cheng Lu, Hui Xie, Xin-Xin Tie, Ruizhe Wang, An-Hua Wu, Feng-Ping Shan
The aim of the work was to investigate the effect and possible mechanism of MENK on the growth of rat C6 glioma in vivo or in vitro. Our findings showed that MENK could inhibit the growth of rat C6 glioma, prolong median survival times in tumor-bearing rats, and induce glioma cell apoptosis. Moreover, MENK could increase the activities of caspase-3, caspase-8 and caspase-9. It also increased the expression of Fas, FasL, Bax, while decreased the expression of Bcl-2. We further confirmed that MENK could increase opioid receptors MOR and DOR expressions, Ca2+ influx into the cytoplasm, and a substantial increase of NFAT1accumulation in the nuclei in C6 glioma cell...
January 8, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29319460/polymorphism-of-opioid-receptors-%C3%AE-1-in-highly-hypnotizable-subjects
#9
Silvano Presciuttini, Michele Curcio, Rosalia Sciarrino, Fabrizio Scatena, Mark P Jensen, Enrica L Santarcangelo
The possible cooperation between hypnotizability-related and placebo mechanisms in pain modulation has not been consistently assessed. Here, we investigate possible genetic bases for such cooperation. The OPRM1 gene, which encodes the μ1 opioid receptor-the primary site of action for endogenous and exogenous opioids-is polymorphic in the general population for the missense mutation Asn40Asp (A118G, rs1799971). The minor allele 118G results in decreased levels of OPRM1 mRNA and protein. As a consequence, G carriers are less responsive to opioids...
January 2018: International Journal of Clinical and Experimental Hypnosis
https://www.readbyqxmd.com/read/29316911/the-standardized-withania-somnifera-dunal-root-extract-alters-basal-and-morphine-induced-opioid-receptor-gene-expression-changes-in-neuroblastoma-cells
#10
Francesca Felicia Caputi, Elio Acquas, Sanjay Kasture, Stefania Ruiu, Sanzio Candeletti, Patrizia Romualdi
BACKGROUND: Behavioral studies demonstrated that the administration of Withania somnifera Dunal roots extract (WSE), prolongs morphine-elicited analgesia and reduces the development of tolerance to the morphine's analgesic effect; however, little is known about the underpinning molecular mechanism(s). In order to shed light on this issue in the present paper we explored whether WSE promotes alterations of μ (MOP) and nociceptin (NOP) opioid receptors gene expression in neuroblastoma SH-SY5Y cells...
January 10, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29302220/a-brief-review-of-the-genetics-and-pharmacogenetics-of-opioid-use-disorders
#11
Wade Berrettini
Increased physician prescribing of opioids to treat chronic nonprogressive pain has been accompanied by an increase in opioid addiction. Twin studies of opioid addiction are consistent with an inherited component of risk, approximately 50%. Several genome-wide association study (GWAS) reports indicate that genetic risk for opioid addiction is conveyed by many alleles of small effect (odds ratios <1.5). These reports have detected alleles in potassium-ion-channel genes (KCNC1 and KCNG2) and in a glutamate receptor auxiliary protein (CNIH3)...
September 2017: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/29296811/randomized-phase-2-trial-of-regadenoson-for-treatment-of-acute-vaso-occlusive-crises-in-sickle-cell-disease
#12
Joshua J Field, Elaine Majerus, Victor R Gordeuk, Michel Gowhari, Carolyn Hoppe, Matthew M Heeney, Maureen Achebe, Alex George, Hillary Chu, Brian Sheehan, Maneka Puligandla, Donna Neuberg, Gene Lin, Joel Linden, David G Nathan
Adenosine A2A receptor (A2AR) agonists have been shown to decrease tissue inflammation induced by hypoxia/reoxygenation in mice with sickle cell disease (SCD). The key mediator of the A2AR agonist's anti-inflammatory effects is a minor lymphocyte subset, invariant natural killer T (iNKT) cells. We tested the hypothesis that administration of an A2AR agonist in patients with SCD would decrease iNKT cell activation and dampen the severity of vaso-occlusive (VO) crises. In a phase 2, randomized, placebo-controlled trial, we administered a 48-hour infusion of the A2AR agonist regadenoson (1...
September 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29276474/experimental-gene-therapy-with-serine-histogranin-and-endomorphin-1-for-the-treatment-of-chronic-neuropathic-pain
#13
Stanislava Jergova, Catherine E Gordon, Shyam Gajavelli, Jacqueline Sagen
The insufficient pain relief provided by current pharmacotherapy for chronic neuropathic pain is a serious medical problem. The enhanced glutamate signaling via NMDA receptors appears to be one of the key events in the development of chronic pain. Although effective, clinical use of systemic NMDA antagonists is limited by adverse effects such as hallucinations and motor dysfunction. Opioids are also potent analgesics but their chronic use is accompanied by tolerance and risk of addiction. However, combination of NMDA antagonists and opioids seems to provide a stable pain relieve at subthreshold doses of both substances, eliminating development of side effects...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29261227/overview-of-microrna-modulation-in-analgesic-research
#14
Sujay Ramanathan, Botros B Shenoda, Seena K Ajit
MicroRNA(miRNA)-mediated gene regulation underlies cellular processes, playing an important role in homeostasis and diseases. The expression and function of miRNAs are altered by various pharmacological agents, with differences in the endogenous levels of miRNAs influencing drug efficacy and toxicity. Thus, miRNA levels could be a biomarker for predicting treatment response, efficacy, and safety. In addition, elucidating the mechanistic significance of miRNA alterations can aid in the identification of therapeutic targets and patient selection, and guide personalized therapy...
December 20, 2017: Current Protocols in Pharmacology
https://www.readbyqxmd.com/read/29259946/genetic-analysis-of-mu-and-kappa-opioid-receptor-and-comt-enzyme-in-cancer-pain-tunisian-patients-under-opioid-treatment
#15
Imen Chatti, Jean-Baptiste Woillard, Amira Mili, Isabelle Creveaux, Ilhem Ben Charfeddine, Jihène Feki, Sarah Langlais, Leila Ben Fatma, Ali Saad, Moez Gribaa, Frédéric Libert
Background: Pain and its opioid treatments are complex measurable traits. Responses to morphine in terms of pain control is likely to be determined by many factors, including the underlying pain sensitivity of the patient, along with nature and extent of the painful process, concomitant medications, genetic and other clinical and environmental factors. This study investigated genetic polymorphisms implicated in the inter-individual pain response variability to opioid treatment in the Tunisian population...
December 2017: Iranian Journal of Public Health
https://www.readbyqxmd.com/read/29258584/lymphocyte-opioid-receptors-as-innovative-biomarkers-of-osteoarthritic-pain-for-the-assessment-and-risk-management-of-opioid-tailored-therapy-before-hip-surgery-to-prevent-chronic-pain-and-opioid-tolerance-addiction-development-opmarkart-opioids-markers-arthroprosthesis
#16
Valentina Malafoglia, Monica Celi, Carolina Muscoli, Sara Ilari, Filomena Lauro, Luigino Antonio Giancotti, Chiara Morabito, Maurizio Feola, Umberto Tarantino, William Raffaeli
BACKGROUND: The incidence of post-surgical chronic pain ranges between 20% and 40% in Europe. Osteoarthritis pain after prosthesis implantation is one of the most severe secondary syndromes, depending not only on surgery but also on organic changes before and after joints replacement. No data are available about risk factors. An excessive inflammatory response plays a central role but a best therapy is not defined yet. It is not clear whether opioid administration could influence post-surgical pain and lead to tolerance or addiction...
December 19, 2017: Trials
https://www.readbyqxmd.com/read/29241501/cyp2d6-drug-gene-and-drug-drug-gene-interactions-among-patients-prescribed-pharmacogenetically-actionable-opioids
#17
Mitchell R Knisely, Janet S Carpenter, Claire Burke Draucker, Todd Skaar, Marion E Broome, Ann M Holmes, Diane Von Ah
PURPOSE: When codeine and tramadol are used for pain management, it is imperative that nurses are able to assess for potential drug-gene and drug-drug-gene interactions that could adversely impact drug metabolism and ultimately pain relief. Both drugs are metabolized through the CYP2D6 metabolic pathway which can be affected by medications as well the patient's own pharmacogenotype. The purpose of this brief report is to identify drug-gene and drug-drug-gene interactions in 30 adult patients prescribed codeine or tramadol for pain...
December 2017: Applied Nursing Research: ANR
https://www.readbyqxmd.com/read/29240768/the-association-between-the-nicotinic-acetylcholine-receptor-%C3%AE-4-subunit-gene-chrna4-rs1044396-and-internet-gaming-disorder-in-korean-male-adults
#18
Jo-Eun Jeong, Je-Keun Rhee, Tae-Min Kim, Su-Min Kwak, Sol-Hee Bang, Hyun Cho, Young-Hoon Cheon, Jung Ah Min, Gil Sang Yoo, Kyudong Kim, Jung-Seok Choi, Sam-Wook Choi, Dai-Jin Kim
The primary aim of this study was to investigate the genetic predisposition of Internet gaming disorder (IGD), and the secondary aim was to compare the results to those of alcohol dependence (AD). Two independent case-control studies were conducted. A total of 30 male participants with IGD, diagnosed according to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, and 30 sex-matched controls participated in study 1. We designed targeted exome sequencing (TES) to test for 72 candidate genes that have been implicated in the pathogenesis of addiction...
2017: PloS One
https://www.readbyqxmd.com/read/29237725/abin-1-negatively-regulates-%C3%AE-opioid-receptor-function
#19
Peilan Zhou, Jiebing Jiang, Hui Yan, Yulei Li, Junru Zhao, Xiao Wang, Ruibin Su, Zehui Gong
The μ-opioid receptor (MOR) is a Gi/o protein-coupled receptor that mediates analgesic, euphoric, and reward effects. Using a bacterial two-hybrid screen, we reported that the carboxyl tail of the rat MOR associates with A20-binding inhibitor of nuclear factor (NF)-κB (ABIN-1) (Zhou et al., 2015). This interaction was confirmed by direct protein - protein binding and co-immunoprecipitation of MOR and ABIN-1 proteins in cell lysates. Saturation binding studies showed that ABIN-1 had no effect on MOR binding...
December 13, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29210332/dopamine-gene-variants-in-opioid-addiction-comparison-of-dependent-patients-nondependent-users-and-healthy-controls
#20
Matthew Randesi, Wim van den Brink, Orna Levran, Vadim Yuferov, Peter Blanken, Jan M van Ree, Jurg Ott, Mary Jeanne Kreek
AIM: To determine whether specific dopaminergic system gene variants are associated with opioid dependence. PATIENTS & METHODS: Subjects included 153 healthy controls, 163 opioid exposed, but not dependent and 281 opioid dependent. Genotypes of 90 variants in 13 genes were examined. RESULTS: The most significant results were obtained for DA β-hydroxylase variants, rs2073837 and rs1611131, which were associated with protection from addiction (q = 0...
December 6, 2017: Pharmacogenomics
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