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https://www.readbyqxmd.com/read/28194850/cannabidiol-reduces-ethanol-consumption-motivation-and-relapse-in-mice
#1
Adrián Viudez-Martínez, María S García-Gutiérrez, Carmen María Navarrón, María Isabel Morales-Calero, Francisco Navarrete, Ana Isabel Torres-Suárez, Jorge Manzanares
This study evaluated the effects of cannabidiol (CBD) on ethanol reinforcement, motivation and relapse in C57BL/6 J mice. The effects of CBD (60 mg/kg, i.p.) on blood ethanol concentration, hypothermia and handling-induced convulsions associated to acute ethanol administration were evaluated. The two-bottle choice paradigm was performed to assess the effects of CBD (30, 60 and 120 mg/kg/day, i.p.) on ethanol intake and preference. In addition, an oral ethanol self-administration experiment was carried out to evaluate the effects of CBD [a single s...
February 13, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28188737/genetic-variation-in-the-behavioral-effects-of-buprenorphine-in-female-mice-derived-from-a-murine-model-of-the-oprm1-a118g-polymorphism
#2
Caroline A Browne, Rebecca L Erickson, Julie A Blendy, Irwin Lucki
Pharmacogenetic studies have identified the non-synonymous single nucleotide polymorphism (A118G) in the human mu opioid receptor (MOR) gene (OPRM1) as a critical genetic variant capable of altering the efficacy of opioid therapeutics. To date few studies have explored the potential impact of the OPRM1 A118G polymorphism on the pharmacological effects of buprenorphine (BPN), a potent MOR partial agonist and kappa opioid receptor antagonist, which is approved by the FDA for the treatment of opioid addiction and chronic pain...
February 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28185645/mu-opioid-receptors-in-gamma-aminobutyric-acidergic-forebrain-neurons-moderate-motivation-for-heroin-and-palatable-food
#3
Pauline Charbogne, Olivier Gardon, Elena Martín-García, Helen L Keyworth, Aya Matsui, Anna E Mechling, Thomas Bienert, Taufiq Nasseef, Anne Robé, Luc Moquin, Emmanuel Darcq, Sami Ben Hamida, Patricia Robledo, Audrey Matifas, Katia Befort, Claire Gavériaux-Ruff, Laura-Adela Harsan, Dominik von Elverfeldt, Jurgen Hennig, Alain Gratton, Ian Kitchen, Alexis Bailey, Veronica A Alvarez, Rafael Maldonado, Brigitte L Kieffer
BACKGROUND: Mu opioid receptors (MORs) are central to pain control, drug reward, and addictive behaviors, but underlying circuit mechanisms have been poorly explored by genetic approaches. Here we investigate the contribution of MORs expressed in gamma-aminobutyric acidergic forebrain neurons to major biological effects of opiates, and also challenge the canonical disinhibition model of opiate reward. METHODS: We used Dlx5/6-mediated recombination to create conditional Oprm1 mice in gamma-aminobutyric acidergic forebrain neurons...
December 26, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/28121474/elevated-levels-of-dna-methylation-at-the-oprm1-promoter-region-in-men-with-opioid-use-disorder
#4
Ghasem Ebrahimi, Gholamreza Asadikaram, Hamed Akbari, Mohammad Hadi Nematollahi, Moslem Abolhassani, Gholamabbas Shahabinejad, Leyla Khodadadnejad, Mohammad Hashemi
BACKGROUND: The mu-opioid receptor, encoded by mu-opioid receptor gene (OPRM1), has an important role in the development of addiction to opioids. Its aberrant reduction on the cell membrane is responsible, at least in part, for tolerance and physical dependence. OBJECTIVES: The present study was designed to identify the relationship between opium consumption and epigenetic mechanisms involved in opium addiction. METHODS: Genomic DNA was extracted from the peripheral blood of 66 men with opium use disorder and 57 healthy men as a control group...
January 25, 2017: American Journal of Drug and Alcohol Abuse
https://www.readbyqxmd.com/read/28115739/genome-wide-association-study-of-therapeutic-opioid-dosing-identifies-a-novel-locus-upstream-of-oprm1
#5
A H Smith, K P Jensen, J Li, Y Nunez, L A Farrer, H Hakonarson, S D Cook-Sather, H R Kranzler, J Gelernter
Opioids are very effective analgesics, but they are also highly addictive. Methadone is used to treat opioid dependence (OD), acting as a selective agonist at the μ-opioid receptor encoded by the gene OPRM1. Determining the optimal methadone maintenance dose is time consuming; currently, no biomarkers are available to guide treatment. In methadone-treated OD subjects drawn from a case and control sample, we conducted a genome-wide association study of usual daily methadone dose. In African-American (AA) OD subjects (n=383), we identified a genome-wide significant association between therapeutic methadone dose (mean=68...
March 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28097908/common-and-specific-genes-and-peripheral-biomarkers-in-children-and-adults-with-attention-deficit-hyperactivity-disorder
#6
Cristian Bonvicini, Stephen V Faraone, Catia Scassellati
OBJECTIVES: Elucidating the biological mechanisms involved in Attention-deficit/hyperactivity disorder (ADHD) has been challenging. Relatively unexplored is the fact that these mechanisms can differ with age. METHODS: We present an overview on the major differences between children and adults with ADHD, describing several studies from genomics to metabolomics performed in ADHD children and in adults. A systematic search (up until February, 2016) was conducted. RESULTS: From a PRISMA flow-chart, a total of eligibility 350 studies from genomics and metabolomics were found for cADHD and 91 for aADHD...
January 18, 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28092646/ex-vivo-nonviral-gene-delivery-of-%C3%AE-opioid-receptor-to-attenuate-cancer-induced-pain
#7
Seiichi Yamano, Chi T Viet, Dongmin Dang, Jisen Dai, Shigeru Hanatani, Tadahiro Takayama, Hironori Kasai, Kentaro Imamura, Ron Campbell, Yi Ye, John C Dolan, William Myung Kwon, Stefan D Schneider, Brian L Schmidt
Virus-mediated gene delivery shows promise for the treatment of chronic pain. However, viral vectors have cytotoxicity. To avoid toxicities and limitations of virus-mediated gene delivery, we developed a novel nonviral hybrid vector: HIV-1 Tat peptide sequence modified with histidine and cysteine residues combined with a cationic lipid. The vector has high transfection efficiency with little cytotoxicity in cancer cell lines including HSC-3 (human tongue squamous cell carcinoma) and exhibits differential expression in HSC-3 (∼45-fold) relative to HGF-1 (human gingival fibroblasts) cells...
February 2017: Pain
https://www.readbyqxmd.com/read/28057931/the-oprm1-a118g-polymorphism-modulates-the-descending-pain-modulatory-system-for-individual-pain-experience-in-young-women-with-primary-dysmenorrhea
#8
Shyh-Yuh Wei, Li-Fen Chen, Ming-Wei Lin, Wei-Chi Li, Intan Low, Ching-Ju Yang, Hsiang-Tai Chao, Jen-Chuen Hsieh
The mu-opioid receptor (OPRM1) A118G polymorphism underpins different pain sensitivity and opioid-analgesic outcome with unclear effect on the descending pain modulatory system (DPMS). Primary dysmenorrhea (PDM), the most prevalent gynecological problem with clear painful and pain free conditions, serves as a good clinical model of spontaneous pain. The objective of this imaging genetics study was therefore to explore if differences in functional connectivity (FC) of the DPMS between the OPRM1 A118G polymorphisms could provide a possible explanation for the differences in pain experience...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28012008/bivariate-genome-wide-association-analyses-identified-genetic-pleiotropic-effects-for-bone-mineral-density-and-alcohol-drinking-in-caucasians
#9
Shan Lu, Lan-Juan Zhao, Xiang-Ding Chen, Christopher J Papasian, Ke-Hao Wu, Li-Jun Tan, Zhuo-Er Wang, Yu-Fang Pei, Qing Tian, Hong-Wen Deng
Several studies indicated bone mineral density (BMD) and alcohol intake might share common genetic factors. The study aimed to explore potential SNPs/genes related to both phenotypes in US Caucasians at the genome-wide level. A bivariate genome-wide association study (GWAS) was performed in 2069 unrelated participants. Regular drinking was graded as 1, 2, 3, 4, 5, or 6, representing drinking alcohol never, less than once, once or twice, three to six times, seven to ten times, or more than ten times per week respectively...
December 23, 2016: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/28006928/sufentanil-and-midazolam-dosing-and-pharmacogenetic-factors-in-pediatric-analgosedation-and-withdrawal-syndrome
#10
K Hronová, P Pokorná, L Posch, O Slanař
Our aim was to describe the effect of dosing and genetic factors on sufentanil- and midazolam-induced analgosedation and withdrawal syndrome (WS) in pediatric population. Analgosedation and withdrawal syndrome development were monitored using COMFORT-neo/-B scores and SOS score. Length of therapy, dosing of sufentanil and midazolam were recorded. Genotypes of selected candidate polymorphisms in CYP3A5, COMT, ABCB1, OPRM1 and PXR were analysed. In the group of 30 neonates and 18 children, longer treatment duration with midazolam of 141 h (2 - 625) vs...
December 21, 2016: Physiological Research
https://www.readbyqxmd.com/read/27964712/genes-associated-with-persistent-lumbar-radicular-pain-a-systematic-review
#11
Siri Bjorland, Aurora Moen, Elina Schistad, Johannes Gjerstad, Cecilie Røe
BACKGROUND: The aim of the present study was to provide an overview of the literature addressing the role of genetic factors and biomarkers predicting pain recovery in newly diagnosed lumbar radicular pain (LRP) patients. METHODS: The search was performed in Medline OVID, Embase, PsycInfo and Web of Science (2004 to 2015). Only prospective studies of patients with LRP addressing the role of genetic factors (genetic susceptibility) and pain biomarkers (proteins in serum) were included...
December 13, 2016: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/27958613/opioid-receptors-in-psoriatic-skin-relationship-with-itch
#12
Piotr Kupczyk, Adam Reich, Marcin Hołysz, Mariusz Gajda, Edyta Wysokińska, Anna Kobuszewska, Dmitry Nevozhay, Beata Nowakowska, Leon Strzadała, Paweł Jagodziński, Jacek C Szepietowski
Psoriasis is an inflammatory immunogenetic skin disease, often accompanied by itch. Opioid receptors are known regulators of itch sensation in the central nervous system. In the brain, μ-opioid receptors may potentiate itch, while activation of κ-opioid receptors may reduce or even alleviate itch; however, the role of opioid receptors in itch perception in the skin is poorly understood. To further elucidate the role of opioid receptors in the neurobiology of psoriatic itch, punch biopsies of non-lesional and lesional skin of patients with psoriasis and healthy controls were studied...
December 13, 2016: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/27958381/a-polymorphism-in-the-oprm1-3-untranslated-region-is-associated-with-methadone-efficacy-in-treating-opioid-dependence
#13
R C Crist, G A Doyle, E C Nelson, L Degenhardt, N G Martin, G W Montgomery, A J Saxon, W Ling, W H Berrettini
The μ-opioid receptor (MOR) is the primary target of methadone and buprenorphine. The primary neuronal transcript of the OPRM1 gene, MOR-1, contains a ~13 kb 3' untranslated region with five common haplotypes in European-Americans. We analyzed the effects of these haplotypes on the percentage of opioid positive urine tests in European-Americans (n=582) during a 24-week, randomized, open-label trial of methadone or buprenorphine/naloxone (Suboxone) for the treatment of opioid dependence. A single haplotype, tagged by rs10485058, was significantly associated with patient urinalysis data in the methadone treatment group...
December 13, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27956669/genetic-polymorphisms-and-their-association-with-the-prevalence-and-severity-of-chronic-postsurgical-pain-a-systematic-review
#14
D M N Hoofwijk, R R I van Reij, B P Rutten, G Kenis, W F Buhre, E A Joosten
BACKGROUND: Although several patient characteristic, clinical, and psychological risk factors for chronic postsurgical pain (CPSP) have been identified, genetic variants including single nucleotide polymorphisms have also become of interest as potential risk factors for the development of CPSP. The aim of this review is to summarize the current evidence on genetic polymorphisms associated with the prevalence and severity of CPSP in adult patients. METHODS: A systematic review of the literature was performed, and additional literature was obtained by reference tracking...
December 2016: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/27955884/pharmacogenetics-guided-analgesics-in-major-abdominal-surgery-further-benefits-within-an-enhanced-recovery-protocol
#15
Anthony J Senagore, Bradley J Champagne, Eslam Dosokey, Justin Brady, Scott R Steele, Harry L Reynolds, Sharon L Stein, Conor P Delaney
OBJECTIVE: Effective, narcotic sparing analgesia is a major component of Enhanced Recovery Protocols (ERP), however the risk of poor analgesia and opioid related side effects (ORADE) remains an issue related to poor outcomes and satisfaction, and is strongly related to the risk of narcotic dependence after surgery. A variety of genes can impact narcotic and non-steroidal (NSAID) drug efficacy including: the CYP family (drug metabolism-narcotics and NSAID), or COMT/ABCB1/OPRM1 (functional receptor and transport activity for analgesia vs side effects)...
November 22, 2016: American Journal of Surgery
https://www.readbyqxmd.com/read/27927796/g9a-inhibits-creb-triggered-expression-of-mu-opioid-receptor-in-primary-sensory-neurons-following-peripheral-nerve-injury
#16
Lingli Liang, Jian-Yuan Zhao, Xiyao Gu, Shaogen Wu, Kai Mo, Ming Xiong, Brianna Marie Lutz, Alex Bekker, Yuan-Xiang Tao
Neuropathic pain, a distressing and debilitating disorder, is still poorly managed in clinic. Opioids, like morphine, remain the mainstay of prescribed medications in the treatment of this disorder, but their analgesic effects are highly unsatisfactory in part due to nerve injury-induced reduction of opioid receptors in the first-order sensory neurons of dorsal root ganglia. G9a is a repressor of gene expression. We found that nerve injury-induced increases in G9a and its catalyzed repressive marker H3K9m2 are responsible for epigenetic silencing of Oprm1, Oprk1, and Oprd1 genes in the injured dorsal root ganglia...
2016: Molecular Pain
https://www.readbyqxmd.com/read/27903758/oprm1-and-comt-gene-gene-interaction-is-associated-with-postoperative-pain-and-opioid-consumption-after-orthopedic-trauma
#17
Heba Khalil, Susan M Sereika, Feng Dai, Sheila Alexander, Yvette Conley, Gary Gruen, Li Meng, Peter Siska, Ivan Tarkin, Richard Henker
BACKGROUND: mu-opioid receptor (OPRM1) and catechol-O-methyltransferase (COMT) contribute to the neurotransmission pathway of pain. COMT affects mu receptor expression and density in the brain. The aim of this study was to explore the OPRM1 and COMT interaction effects on postoperative pain and opioid consumption. METHODS: This cross-sectional exploratory study used genotype and clinical data from 153 postoperative patients. Using multiple regression analyses, four single-nucleotide polymorphisms of COMT (rs6269, rs4633, rs4818, and rs4680), their haplotypes, and diplotypes were considered for their interactions with A118G of OPRM1 regarding postoperative pain and opioid consumption...
November 30, 2016: Biological Research for Nursing
https://www.readbyqxmd.com/read/27826798/contribution-of-pharmacogenetic-testing-to-modeled-medication-change-recommendations-in-a-long-term-care-population-with-polypharmacy
#18
Elaine A Sugarman, Ali Cullors, Joel Centeno, David Taylor
BACKGROUND: Among long-term care facility residents, polypharmacy is common, and often appropriate, given the need to treat multiple, complex, chronic conditions. Polypharmacy has, however, been associated with increased healthcare costs, adverse drug events, and drug interactions. The current study evaluates the potential medication cost savings of adding personalized pharmacogenetic information to traditional medication management strategies. METHODS: One hundred and twelve long-term care residents completed pharmacogenetic testing for targeted variants in the following genes: CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4/CYP3A5, HTR2A, HTR2C, SLC6A4, SLC6A2 COMT, OPRM1, SLCO1B1, VKORC1 and MTHFR...
December 2016: Drugs & Aging
https://www.readbyqxmd.com/read/27818236/a-role-for-the-mu-opioid-receptor-in-the-antidepressant-effects-of-buprenorphine
#19
Shivon A Robinson, Rebecca L Erickson, Caroline A Browne, Irwin Lucki
Buprenorphine (BPN), a mixed opioid drug with high affinity for mu (MOR) and kappa (KOR) opioid receptors, has been shown to produce behavioral responses in rodents that are similar to those of antidepressant and anxiolytic drugs. Although recent studies have identified KORs as a primary mediator of BPN's effects in rodent models of depressive-like behavior, the role of MORs in BPN's behavioral effects has not been as well explored. The current studies investigated the role of MORs in mediating conditioned approach behavior in the novelty-induced hypophagia (NIH) test, a behavioral measure previously shown to be sensitive to chronic treatment with antidepressant drugs...
February 15, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/27759945/dna-methylation-and-alcohol-use-disorders-progress-and-challenges
#20
Huiping Zhang, Joel Gelernter
BACKGROUND AND OBJECTIVES: Risk for alcohol use disorders (AUDs) is influenced by gene-environment interactions. Environmental factors can affect gene expression through epigenetic mechanisms such as DNA methylation. This review outlines the findings regarding the association of DNA methylation and AUDs. METHODS: We searched PubMed (by April 2016) and identified 29 studies that examined the association of DNA methylation and AUDs. We also evaluated the methods used in these studies...
October 19, 2016: American Journal on Addictions
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