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https://www.readbyqxmd.com/read/28429582/obesity-and-addiction-can-a-complication-of-surgery-help-us-understand-the-connection
#1
REVIEW
V Ivezaj, L E Stoeckel, N M Avena, S C Benoit, A Conason, J F Davis, A N Gearhardt, R Goldman, J E Mitchell, C N Ochner, K K Saules, K J Steffen, E Stice, S Sogg
Obesity is a multifactorial, chronic disease that has proven difficult to treat. An increased understanding of aetiological mechanisms is critical to the development of more effective obesity prevention and treatment strategies. A growing body of empirical evidence has demonstrated parallels between obesity, overeating and substance abuse, including shared behavioural, psychological and neurophysiological factors implicated in the excessive intake of both food and substances of abuse. Several different lines of research have recently emerged that hold the potential to shed light on the connection between obesity, food reward and addiction, with studies examining changes in alcohol use/misuse after weight loss surgery providing a particularly interesting perspective on these interrelationships...
April 21, 2017: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28417948/erbb-family-signalling-a-paradigm-for-oncogene-addiction-and-personalized-oncology
#2
REVIEW
Nico Jacobi, Rita Seeboeck, Elisabeth Hofmann, Andreas Eger
ErbB family members represent important biomarkers and drug targets for modern precision therapy. They have gained considerable importance as paradigms for oncoprotein addiction and personalized medicine. This review summarizes the current understanding of ErbB proteins in cell signalling and cancer and describes the molecular rationale of prominent cases of ErbB oncoprotein addiction in different cancer types. In addition, we have highlighted experimental technologies for the development of innovative cancer cell models that accurately predicted clinical ErbB drug efficacies...
April 12, 2017: Cancers
https://www.readbyqxmd.com/read/28412411/mirtazapine-and-ketanserin-alter-preference-for-gambling-like-schedules-of-reinforcement-in-rats
#3
Amanda L Persons, Stephanie E Tedford, T Celeste Napier
Drug and behavioral addictions have overlapping features, e.g., both manifest preference for larger, albeit costlier, reinforcement options in cost/benefit decision-making tasks. Our prior work revealed that the mixed-function serotonergic compound, mirtazapine, attenuates behaviors by rats motivated by abused drugs. To extend this work to behavioral addictions, here we determined if mirtazapine and/or ketanserin, another mixed-function serotonin-acting compound, can alter decision-making in rats that is independent of drug (or food)-motivated reward...
April 12, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28391178/mirtazapine-attenuates-cocaine-seeking-in-rats
#4
Susana Barbosa-Méndez, Phillipe Leff, Adriana Arías-Caballero, Ricardo Hernández-Miramontes, Gerardo Heinze, Alberto Salazar-Juárez
BACKGROUND: Relapse to cocaine use is a major problem in the clinical treatment of cocaine addiction. Antidepressants have been studied for their therapeutic potential to treat cocaine use disorder. Research has suggested that antidepressants attenuate both drug craving and the re-acquisition of drug-seeking and drug-taking behaviors. This study examined the efficacy of mirtazapine, an antidepressant/anxiolytic, in decreasing cocaine seeking in rats. METHODS: We used the cocaine self-administration paradigm to assess the effects of mirtazapine on rats trained to self-administer cocaine or food under a fixed-ratio schedule...
April 4, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28388533/brca1-haploinsufficiency-cell-autonomously-activates-rankl-expression-and-generates-denosumab-responsive-breast-cancer-initiating-cells
#5
Elisabet Cuyàs, Bruna Corominas-Faja, María Muñoz-San Martín, Begoña Martin-Castillo, Ruth Lupu, Joan Brunet, Joaquim Bosch-Barrera, Javier A Menendez
Denosumab, a monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL), might be a novel preventative therapy for BRCA1-mutation carriers at high risk of developing breast cancer. Beyond its well-recognized bone-targeted activity impeding osteoclastogenesis, denosumab has been proposed to interfere with the cross-talk between RANKL-producing sensor cells and cancer-initiating RANK+ responder cells that reside within premalignant tissues of BRCA1-mutation carriers. We herein tested the alternative but not mutually exclusive hypothesis that BRCA1 deficiency might cell-autonomously activate RANKL expression to generate cellular states with cancer stem cell (CSC)-like properties...
March 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28385503/novel-small-molecule-guanidine-sigma1-inhibitors-for-advanced-prostate-cancer
#6
Joseph M Salvino, Yellamelli V V Srikanth, Rongliang Lou, Halley M Oyer, Nan Chen, Felix J Kim
Prostate cancer is the most frequently diagnosed malignancy and the leading cause of cancer related death in men. First line therapy for disseminated disease relies on androgen deprivation, leveraging the addiction of these tumors on androgens for both growth and survival. Treatment typically involves antagonizing the androgen receptor (AR) or blocking the synthesis of androgens. Recurrence is common and within 2-3years patients develop castration resistant tumors that become unresponsive to AR-axis targeted therapies...
March 18, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28382542/kk-92a-a-novel-gabab-receptor-positive-allosteric-modulator-attenuates-nicotine-self-administration-and-cue-induced-nicotine-seeking-in-rats
#7
Xia Li, Emmanuel Sturchler, Katarzyna Kaczanowska, Michael Cameron, M G Finn, Patrick Griffin, Patricia McDonald, Athina Markou
RATIONALE: GABAB receptors (GABABR) play a critical role in GABAergic neurotransmission in the brain and are thought to be one of the most promising targets for the treatment of drug addiction. GABABR positive allosteric modulators (PAMs) have shown promise as potential anti-addictive therapies, as they lack the sedative and muscle relaxant properties of full GABAB receptor agonists such as baclofen. OBJECTIVES: The present study was aimed at developing novel, selective, and potent GABABR PAMs with efficacy on abuse-related effects of nicotine...
April 5, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28379862/vermont-hub-and-spoke-model-of-care-for-opioid-use-disorder-development-implementation-and-impact
#8
John R Brooklyn, Stacey C Sigmon
BACKGROUND: Opioid use disorders (OUDs) are reaching epidemic proportions in the United States, and many geographic areas struggle with a persistent shortage in availability of opioid agonist treatment. Over the past 5 years, Vermont addiction medicine physicians and public health leaders have responded to these challenges by developing an integrated hub-and-spoke opioid treatment network. METHODS: In the present report, we review the development, implementation, and impact of this novel hub-and-spoke model for expanding OUD treatment in Vermont...
April 4, 2017: Journal of Addiction Medicine
https://www.readbyqxmd.com/read/28378414/oxytocin-and-opioid-addiction-revisited-old-drug-new-applications
#9
REVIEW
Panos Zanos, Polymnia Georgiou, Carol Weber, Fiona Robinson, Christos Kouimtsidis, Ramin Niforooshan, Alexis Bailey
Opioid addiction has devastating health and socio-economic consequences, and current pharmacotherapy is limited and often accompanied by side effects, thus novel treatment is warranted. Traditionally, the neurohypophyseal peptide oxytocin (OT) is known for its effects on mediating reward, social affiliation and bonding, stress and learning and memory. There is now strong evidence that OT is a possible candidate for the treatment of drug addiction and depression-addiction co-morbidities. This review summarizes and critically discusses the preclinical evidence surrounding the consequences of pharmacological manipulation of the oxytocinergic system on opioid addiction-related processes, as well as the effects of opioids on the OT system at different stages of the addiction cycle...
April 5, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28371816/evaluation-of-an-integrated-multidisciplinary-program-to-address-unsafe-use-of-opioids-prescribed-for-pain
#10
William C Becker, Sara N Edmond, Dana J Cervone, Ajay Manhapra, John J Sellinger, Brent A Moore, Ellen L Edens
Objectives. : Unsafe use of opioids prescribed for pain is a common challenge in primary care. We aimed to describe a novel clinical program designed to address this issue-the Opioid Reassessment Clinic-and evaluate preliminary efficacy. Methods. : The Opioid Reassessment Clinic is a multidisciplinary care team staffed by an internist, addiction psychiatrist, advanced practice nurse, and health psychologist designed to perform enhanced assessment and longitudinal treatment of patients with unsafe use of opioids prescribed for pain...
March 23, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28357460/naltrexone-moderates-the-relationship-between-cue-induced-craving-and-subjective-response-to-methamphetamine-in-individuals-with-methamphetamine-use-disorder
#11
Daniel J O Roche, Matthew J Worley, Kelly E Courtney, Spencer Bujarski, Edythe D London, Steven Shoptaw, Lara A Ray
RATIONALE: Reductions in cue-induced craving and subjective response to drugs of abuse are commonly used as initial outcome measures when testing novel medications for the treatment of addiction. Yet neither the relationship between these two measures at the individual level nor the moderating effects of pharmacotherapies on this relationship has been examined. OBJECTIVE: This secondary data analysis sought to examine (1) the predictive relationship between cue-induced craving and subsequent acute subjective response to methamphetamine (MA) and (2) whether the opioid-receptor antagonist naltrexone moderated this association in a sample of non-treatment-seeking individuals who met DSM-IV criteria for MA use disorder (abuse or dependence)...
March 29, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28357120/gabab-receptor-allosteric-modulators-exhibit-pathway-dependent-and-species-selective-activity
#12
Emmanuel Sturchler, Xia Li, Maria de Lourdes Ladino, Kasia Kaczanowska, Michael Cameron, Patrick R Griffin, M G Finn, Athina Markou, Patricia McDonald
Positive modulation of the GABAB receptor (GABABR) represents a potentially useful therapeutic approach for the treatment of nicotine addiction. The positive allosteric modulators (PAMs) of GABABR GS39783 and BHF177 enhance GABA-stimulated [(35)S]GTP γS-binding, and have shown efficacy in a rodent nicotine self-administration procedure reflecting aspects of nicotine dependence. Interestingly, the structural related analog, NVP998, had no effect on nicotine self-administration in rats despite demonstrating similar pharmacokinetic properties...
April 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28356897/novel-molecular-strategies-and-targets-for-opioid-drug-discovery-for-the-treatment-of-chronic-pain
#13
REVIEW
Keith M Olson, Wei Lei, Attila Keresztes, Justin LaVigne, John M Streicher
Opioid drugs like morphine and fentanyl are the gold standard for treating moderate to severe acute and chronic pain. However, opioid drug use can be limited by serious side effects, including constipation, tolerance, respiratory suppression, and addiction. For more than 100 years, we have tried to develop opioids that decrease or eliminate these liabilities, with little success. Recent advances in understanding opioid receptor signal transduction have suggested new possibilities to activate the opioid receptors to cause analgesia, while reducing or eliminating unwanted side effects...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28346058/promising-pharmacogenetic-targets-for-treating-alcohol-use-disorder-evidence-from-preclinical-models
#14
Jennifer A Rinker, Patrick J Mulholland
Inherited genetic variants contribute to risk factors for developing an alcohol use disorder, and polymorphisms may inform precision medicine strategies for treating alcohol addiction. Targeting genetic mutations linked to alcohol phenotypes has provided promising initial evidence for reducing relapse rates in alcoholics. Although successful in some studies, there are conflicting findings and the reports of adverse effects may ultimately limit their clinical utility, suggesting that novel pharmacogenetic targets are necessary to advance precision medicine approaches...
March 27, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28340145/human-abuse-potential-of-the-new-opioid-analgesic-molecule-nktr-181-compared-with-oxycodone
#15
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
https://www.readbyqxmd.com/read/28332047/mechanisms-of-resistance-to-target-therapies-in-non-small-cell-lung-cancer
#16
Francesco Facchinetti, Claudia Proto, Roberta Minari, Marina Garassino, Marcello Tiseo
Targeted therapies are revolutionizing the treatment of advanced non-small cell lung cancer (NSCLC). The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements, has changed the treatment landscape while improving the prognosis of lung cancer patients. Inevitably, virtually all patients initially treated with targeted therapies develop resistance because of the emergence of an insensitive cellular population, selected by pharmacologic pressure. Diverse mechanisms of resistance, in particular to EGFR, ALK and ROS1 tyrosine-kinase inhibitors (TKIs), have now been discovered and may be classified in three different groups: (1) alterations in the target (such as EGFR T790M and ALK or ROS1 mutations); (2) activation of alternative pathways (i...
March 23, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28326026/pre-clinical-studies-with-d-penicillamine-as-a-novel-pharmacological-strategy-to-treat-alcoholism-updated-evidences
#17
REVIEW
Alejandro Orrico, Lucía Martí-Prats, María J Cano-Cebrián, Luis Granero, Ana Polache, Teodoro Zornoza
Ethanol, as other drugs of abuse, is able to activate the ventral tegmental area dopamine (VTA-DA) neurons leading to positively motivational alcohol-seeking behavior and use, and, ultimately to ethanol addiction. In the last decades, the involvement of brain-derived acetaldehyde (ACD) in the ethanol actions in the mesolimbic pathway has been widely demonstrated. Consistent published results have provided a mechanistic support to the use of ACD inactivating agents to block the motivational and reinforcing properties of ethanol...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28323108/chronic-methamphetamine-exposure-significantly-decreases-microglia-activation-in-the-arcuate-nucleus
#18
Steven A Lloyd, Beau Corkill, Matthew C Bruster, Rick L Roberts, Ryan A Shanks
Methamphetamine is a powerful psychostimulant drug and its use and abuse necessitates a better understanding of its neurobiobehavioral effects. The acute effects of binge dosing of methamphetamine on the neurons in the CNS are well studied. However, the long-term effects of chronic, low-dose methamphetamine are less well characterized, especially in other cell types and areas outside of the major dopamine pathways. Mice were administered 5mg/kg/day methamphetamine for ten days and brain tissue was analyzed using histochemistry and image analysis...
March 18, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28322982/toward-biomarkers-of-the-addicted-human-brain-using-neuroimaging-to-predict-relapse-and-sustained-abstinence-in-substance-use-disorder
#19
REVIEW
Scott J Moeller, Martin P Paulus
The ability to predict relapse is a major goal of drug addiction research. Clinical and diagnostic measures are useful in this regard, but these measures do not fully and consistently identify who will relapse and who will remain abstinent. Neuroimaging approaches have the potential to complement these standard clinical measures to optimize relapse prediction. The goal of this review was to survey the existing drug addiction literature that either used a baseline functional or structural neuroimaging phenotype to longitudinally predict a clinical outcome, or that examined test-retest of a neuroimaging phenotype during a course of abstinence or treatment...
March 18, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28315272/sigma-receptors-and-substance-use-disorders
#20
Valentina Sabino, Callum Hicks, Pietro Cottone
Thanks to advances in neuroscience, addiction is now recognized as a chronic brain disease with genetic, developmental, and cultural components. Drugs of abuse, including alcohol, are able to produce significant neuroplastic changes responsible for the profound disturbances shown by drug addicted individuals. The current lack of efficacious pharmacological treatments for substance use disorders has encouraged the search for novel and more effective pharmacotherapies. Growing evidence strongly suggests that Sigma Receptors are involved in the addictive and neurotoxic properties of abused drugs, including cocaine , methamphetamine , and alcohol...
2017: Advances in Experimental Medicine and Biology
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