DOCSLIB.ORG

The Kappa Opioid Receptor: from Addiction to Depression, and Back Laurence Lalanne, Gulebru Ayranci, Brigitte Kieffer, Pierre-Eric Lutz

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Kappa Opioid Receptor: from Addiction to Depression, and Back Laurence Lalanne, Gulebru Ayranci, Brigitte Kieffer, Pierre-Eric Lutz The Kappa Opioid Receptor: From Addiction to Depression, and Back Laurence Lalanne, Gulebru Ayranci, Brigitte Kieffer, Pierre-Eric Lutz To cite this version: Laurence Lalanne, Gulebru Ayranci, Brigitte Kieffer, Pierre-Eric Lutz. The Kappa Opioid Recep- tor: From Addiction to Depression, and Back. Frontiers in Psychiatry, Frontiers, 2014, 5, pp.170. 10.3389/fpsyt.2014.00170. hal-02437500 HAL Id: hal-02437500 https://hal.archives-ouvertes.fr/hal-02437500 Submitted on 14 Jan 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. REVIEW ARTICLE published: 08 December 2014 PSYCHIATRY doi: 10.3389/fpsyt.2014.00170 The kappa opioid receptor: from addiction to depression, and back 1,2† 1,3† 3 3 Laurence Lalanne , Gulebru Ayranci , Brigitte L. Kieffer and Pierre-Eric Lutz * 1 CNRS UMR-7104, Translational Medicine and Neurogenetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U-964, Université de Strasbourg, Illkirch, France 2 Department of Psychiatry, University Hospital of Strasbourg and Medical School of Strasbourg, Strasbourg, France 3 Douglas Mental Health Institute, McGill University, Montréal, QC, Canada Edited by: Comorbidity is a major issue in psychiatry that notably associates with more severe symp- Caitlin Elissa McOmish, Columbia toms, longer illness duration, and higher service utilization. Therefore, identifying key University, USA clusters of comorbidity and exploring the underlying pathophysiological mechanisms repre- Reviewed by: Michael R. Bruchas, Washington sent important steps toward improving mental health care. In the present review, we focus University in St. Louis, USA on the frequent association between addiction and depression. In particular, we summarize Heather Madsen, Florey Institute of the large body of evidence from preclinical models indicating that the kappa opioid recep- Neuroscience & Mental Health, tor (KOR), a member of the opioid neuromodulatory system, represents a central player Australia in the regulation of both reward and mood processes. Current data suggest that the KOR *Correspondence: modulates overlapping neuronal networks linking brainstem monoaminergic nuclei with Pierre-Eric Lutz, McGill Group for Suicide Studies, Douglas Mental forebrain limbic structures. Rewarding properties of both drugs of abuse and natural stim- Health Institute, McGill University, uli, as well as the neurobiological effects of stressful experiences, strongly interact at the 6875, Boulevard La Salle, Montréal, level of KOR signaling. In addiction models, activity of the KOR is potentiated by stressors QC H4H 1R3 Canada e-mail: [email protected] and critically controls drug-seeking and relapse. In depression paradigms, KOR signaling †Laurence Lalanne and Gulebru is responsive to a variety of stressors, and mediates despair-like responses. Altogether, Ayranci have contributed equally to the KOR represents a prototypical substrate of comorbidity, whereby life experiences con- this work. verge upon common brain mechanisms to trigger behavioral dysregulation and increased risk for distinct but interacting psychopathologies. Keywords: kappa opioid receptor, place conditioning, reward, addiction, anhedonia, depression, comorbidity, animal models INTRODUCTION peptides to inhibit neuronal activity. Among opioid peptides, Addiction and depression are chronic relapsing disorders with dev- dynorphins (encoded by the Pdyn gene) primarily activate the astating consequences for individuals and their social environment KOR and have very low affinity for MOR or DOR. Conversely, (1). Chronic exposure to drugs of abuse, as well as prolonged the other opioid peptides (endorphin and enkephalins) poorly abstinence from these drugs, is strongly associated with lowered interact with the KOR. Therefore, the dynorphin/KOR signaling mood and a negative affective state. Conversely, in some individu- pathway forms a distinct process within the opioid system (4, 5). als, depressed mood potently drives the consumption of euphoric Opioid receptors tightly regulate motivational processes, and psychoactive substances, a process referred to as self-medication. are identified as important players in psychiatric disorders char- Accordingly, epidemiological studies have clearly demonstrated acterized by reward dysfunction, such as addiction and depression a marked comorbidity between addiction and depression (2, 3). (6, 7). Several exhaustive reviews have recently summarized data This comorbidity is accompanied by greater functional disabil- on the role of MOR and DOR in these disorders, and will be ity, longer illness duration, less social competence, and higher briefly mentioned when appropriate (6, 8–11). Our goal is to service utilization. Therefore, understanding pathophysiological provide the reader with a historical and neuro-anatomical per- mechanisms underlying comorbidity has important therapeutic spective on where, when, and how KORs are recruited in rodent implications. models of addiction and stress-related psychopathology (12–16). The present review will discuss numerous lines of evidence First, we will summarize how the KOR progressively emerged as that have accumulated to document the kappa opioid recep- an anti-reward system that encodes dysphoria and limits motiva- tor (KOR) as an important substrate in comorbidity between tional properties of drugs of abuse. Secondly, we will show that addictive and depressive disorders. The KOR belongs to the opi- the KOR is recruited and activated during stressful experiences, oid system, a neuromodulatory system that is widely expressed thereby contributing to the emergence of depressive states (10, 17, throughout the central and peripheral nervous systems. The opi- 18). Finally, we will discuss two main aspects of how these roles oid system is composed of three G protein-coupled opioid recep- of KOR in addiction, stress-related behaviors and depression have tors: mu (MOR), delta (DOR), and kappa (KOR), which under important implications for the understanding of comorbidity. On physiological conditions are activated by a family of endogenous one hand, we will show that stress-induced recruitment of KOR www.frontiersin.org December 2014 | Volume 5 | Article 170 | 1 Lalanne et al. The kappa opioid receptor in addiction and depression signaling is a potent trigger of drug-seeking and relapsing behav- iors. On the other hand, we will summarize data on KOR function in the particular context of depressive-like behaviors that emerge during chronic exposure to drugs of abuse, as well as during drug abstinence (19–21). As a pathophysiological substrate of comorbidity, the KOR rep- resents a promising pharmacological target (10, 18). Clinical trials are currently on-going to assess KOR antagonists as a treatment for depression (22), in particular in the context of addicted patients suffering from comorbid depressive conditions (23, 24). Build- ing on rodent studies, we will discuss the potential of therapeutic strategies targeting the KOR. KAPPA OPIOID RECEPTOR: AN ANTI-REWARD, DYSPHORIC SYSTEM Interest in KOR pharmacology historically stemmed from the hope of developing analgesic compounds devoid of the classical abuse potential of MOR agonists, such as morphine. Unfortunately, early human studies exploring properties of KOR agonists reported potent dysphoric and psychomimetic effects (25, 26). While these results clearly decreased the therapeutic potential of KOR in the treatment of pain,they also urged preclinical researchers to explore FIGURE 1 | A simplified scheme of neuronal circuits implicated in the regulation of reward (green) and stress (orange), which are both these intriguing dysphoric effects. modulated by dynorphins and the kappa opioid receptor (KOR). Activation of the MOR is known to induce euphoria in KOR-mediated inhibition of ventral tegmental area (VTA) dopaminergic human, and to produce reinforcement in animal models. There- neurons projecting to the prefrontal cortex (PFC) is responsible for dysphoria and conditioned place aversion (13, 27, 33). Dynorphinergic fore, researchers hypothesized that MOR and KOR may have opposite effects in the regulation of motivational processes, poten- medium spiny neurons, located in the nucleus accumbens (NAc) and expressing D1 dopamine receptors, send axonal projections back to the tially through the modulation of common neuronal pathways. VTA (36), further supporting the importance of KOR in dopamine This framework was initially explored using conditioned place modulation and as an anti-reward agent. In addition, stressful experiences preference (CPP) or conditioned place avoidance (CPA). In this trigger widespread corticotropin releasing factor (CRF) release in the central nervous system (37), leading to dynorphin release and KOR Pavlovian conditioning paradigm, a drug is repeatedly paired with a set of environmental stimuli that progressively acquire posi- phosphorylation, notably in the dorsal raphe nucleus (DRN) (38) and locus coeruleus (LC) (39). Stress-induced signaling events have been extensively tive (CPP) or negative
Load more

Recommended publications
  • Distinct Mu, Delta, and Kappa Opioid Receptor Mechanisms Underlie Low Sociability and Depressive-Like Behaviors During Heroin Abstinence
    Neuropsychopharmacology (2014) 39, 2694–2705 & 2014 American College of Neuropsychopharmacology. All rights reserved 0893-133X/14 www.neuropsychopharmacology.org Distinct Mu, Delta, and Kappa Opioid Receptor Mechanisms Underlie Low Sociability and Depressive-Like Behaviors During Heroin Abstinence ,1,2 1 1 1 1 Pierre-Eric Lutz* , Gulebru Ayranci , Paul Chu-Sin-Chung , Audrey Matifas , Pascale Koebel , 1 1 1 ,1,3 Dominique Filliol , Katia Befort , Abdel-Mouttalib Ouagazzal and Brigitte L Kieffer* 1Translational Medicine and Neurogenetics, Institut de Ge´ne´tique et de Biologie Mole´culaire et Cellulaire, INSERM U-964, CNRS UMR-7104, 2 Universite´ de Strasbourg, Illkirch, France; McGill Group for Suicide Studies, Douglas Institute Research Centre, McGill University, Montre´al, 3 Que´bec, Canada; Douglas Institute Research Centre, McGill University, Montre´al, Que´bec, Canada Addiction is a chronic disorder involving recurring intoxication, withdrawal, and craving episodes. Escaping this vicious cycle requires maintenance of abstinence for extended periods of time and is a true challenge for addicted individuals. The emergence of depressive symptoms, including social withdrawal, is considered a main cause for relapse, but underlying mechanisms are poorly understood. Here we establish a mouse model of protracted abstinence to heroin, a major abused opiate, where both emotional and working memory deficits unfold. We show that delta and kappa opioid receptor (DOR and KOR, respectively) knockout mice develop either stronger or reduced emotional disruption during heroin abstinence, establishing DOR and KOR activities as protective and vulnerability factors, respectively, that regulate the severity of abstinence. Further, we found that chronic treatment with the antidepressant drug fluoxetine prevents emergence of low sociability, with no impact on the working memory deficit, implicating serotonergic mechanisms predominantly in emotional aspects of abstinence symptoms.
    [Show full text]
  • Dr Michael Bruchas Michael Bruchas’S Research Training Is in GPCR Pharmacology and Neuroscience
    INRC 2014 Awardees Dr Brigitte Kieffer B. L. Kieffer is Professor at McGill Univerity and at the Université de Strasbourg France. Her team uses mouse genetic approaches to tacKle the role of opioid receptors in brain physiology and disorders, and to search for novel genes involved in psychiatric disorders. She has developed and shared exquisite genetic tools worldwide, and has developed innovative research lines with strong impact in neuroscience and biomedical research. Her worK has important implications for the development of treatment of pain, drug abuse and emotional disorders. She is part of the Center for Opioid Receptors and Drugs of Abuse or CSORDA. Pr. Kieffer is recipient of the Jules Martin (French Academy of Science, 2001) and the Lounsbery (French and US Academies of Science, 2004) Awards, and has become an EMBO Member in 2009. In 2012 she received the Lamonica Award of Neurology (French Academy of Science) and was nominated Chevalier de la Légion lecture d’honneur. In December 2013 she was elected as a member of the French Academy of Sciences. She started as the Scientific Director of the Douglas Hospital Research Centre, affiliated to McGill University in January 2014. Dr Christopher Evans Christopher Evans received his Ph.D. from Imperial College London, conducting his Founder’s thesis research on endorphins and enkephalins, at the Medical Research Council Institute in Mill Hill. After a postdoctoral fellowship at Stanford University, he joined the UCLA faculty in the Department of Psychiatry and Biobehavioral Science. His research accomplishments have included identification of a number of novel endogenous opioid peptides and the cloning of the first opioid receptor.
    [Show full text]
  • Role of Mu-Opioid Receptors in the Behavioral Effects of the Antidepressant
    Role of Mu-Opioid Receptors in the Behavioral Effects of the Antidepressant Tianeptine Jaena Han Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy under the Executive Committee of the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2021 © 2021 Jaena Han All Rights Reserved Abstract Role of Mu-Opioid Receptors in the Behavioral Effects of the Antidepressant Tianeptine Jaena Han For over half a century, the monoamine hypothesis has been the dominant theoretical framework guiding depression research and drug development. This hypothesis posits that depression arises from a deficiency in the monoaminergic neurotransmitters serotonin, norepinephrine, and possibly dopamine, and that antidepressants function by increasing extracellular availability of these monoamines in the brain, especially at the synaptic level. It is clear however, that the monoamine hypothesis cannot fully explain either the pathophysiology of depression nor the mechanisms of antidepressant action. Tianeptine is an atypical antidepressant used in Europe to treat patients who respond poorly to selective serotonin reuptake inhibitors (SSRIs). The recent discovery that tianeptine is a mu opioid receptor (MOR) and delta opioid receptor (DOR) agonist has provided a potential avenue for expanding our understanding of antidepressant treatment beyond the monoamine hypothesis. This dissertation aims to understand the neural circuits underlying tianeptine’s antidepressant effects. We first characterized the acute and chronic effects of tianeptine on depressive-like and other opioid-related behaviors in mice, and used genetic and pharmacological models to test whether these behavioral effects are mediated by MOR and/or DOR. We found that acute tianeptine administration produced an antidepressant-like reduction in immobility time in the forced swim test, as well as classic opioid-like effects including analgesia, hypophagia, hyperactivity, and conditioned place preference.
    [Show full text]
  • Emotional Impairment and Persistent Upregulation of Mglu5 Receptor Following Morphine Abstinence
    International Journal of Neuropsychopharmacology, (2016) 19(7): 1–10 doi:10.1093/ijnp/pyw011 Advance Access Publication: February 9, 2016 Research Article research article Emotional Impairment and Persistent Upregulation of mGlu5 Receptor following Morphine Abstinence: Implications of an mGlu5-MOPr Interaction Panos Zanos, PhD; Polymnia Georgiou, PhD; Loreto Rojo Gonzalez, BSc; Susanna Hourani, PhD; Ying Chen, PhD; Ian Kitchen, PhD; Brigitte L Kieffer, PhD; Raphaelle Winsky-Sommerer, PhD; Alexis Bailey, PhD School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK (Dr Zanos, Dr Georgiou, Ms Rojo Gonzalez, Prof. Hourani, Prof. Kitchen, Dr Winsky-Sommerer, and Dr Bailey); Department of Psychiatry, University of Maryland, School of Medicine, Baltimore, MD (Dr Zanos and Dr Georgiou); Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK (Dr Chen); Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Illkirch, France (Prof. Kieffer); Douglas Hospital Research Center, Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, Quebec, Canada (Prof. Kieffer); Institute of Medical and Biomedical Education, St George’s University of London, London (Dr Bailey). P.Z. and P.G. contributed equally to this work. Correspondence: Alexis Bailey, PhD, Institute of Medical and Biomedical Education, St George’s University of London, London SW17 0RE, UK (abailey@ sgul.ac.uk). Abstract Background: A difficult problem in treating opioid addicts is the maintenance of a drug-free state because of the negative emotional symptoms associated with withdrawal, which may trigger relapse.
    [Show full text]
  • 50 Years of INRC: 1969 to 2019 – 55 Years of Our Rockefeller University Research and 50 to 60 Years of Opioid Research Mary Jeanne Kreek, M.D
    50 Years of INRC: 1969 to 2019 – 55 Years of our Rockefeller University Research and 50 to 60 Years of Opioid Research Mary Jeanne Kreek, M.D. Patrick E. and Beatrice M. Haggerty Professor Head of Laboratory The Laboratory of the Biology of Addictive Diseases The Rockefeller University Senior Physician, The Rockefeller University Hospital International Narcotics Research Conference July 8, 2019 New York, NY Funded primarily by Dr. Miriam and Sheldon Adelson Medical Research Foundation, NIH-NIDA, NIH-NIAAA, NIH-CRR, Tri-Institutional Therapeutics Discovery Institute, Robertson Therapeutic Development Fund, and others International Narcotics Research Conference Founders Lecturers (First Awardee 1999) 1999 Eric J. Simon 2009 R. Alan North 2000 Brian M. Cox 2010 Masamichi Satoh 2001 Philip S. Portoghese 2011 Charles Chavkin 2002 Lars Terenius 2012 F. Ivy Carroll 2003 Bernard Roques 2013 Graeme Henderson 2004 Ji-Sheng Han 2014 Christopher Evans 2005 Mary Jeanne Kreek Brigitte Kieffer 2006 Huda Akil 2015 Gavril Pasternak (d. 2019) Stan Watson 2016 Lakshmi Devi 2007 Volker Hoellt 2017 John Traynor Horace Loh 2018 Macdonald Christie 2008 Jan van Ree 2019 Sol Snyder Kreek 2019 International Narcotics Research Conference Founders Lecturers at this 50th Anniversary Meeting 1999 Eric J. Simon 2009 R. Alan North 2000 Brian M. Cox 2010 Masamichi Satoh 2001 Philip S. Portoghese 2011 Charles Chavkin 2002 Lars Terenius 2012 F. Ivy Carroll 2003 Bernard Roques 2013 Graeme Henderson 2004 Ji-Sheng Han 2014 Christopher Evans 2005 Mary Jeanne Kreek Brigitte Kieffer 2006 Huda Akil 2015 Gavril Pasternak (d. 2019) Stan Watson 2016 Lakshmi Devi 2007 Volker Hoellt 2017 John Traynor Horace Loh 2018 Macdonald Christie 2008 Jan van Ree 2019 Sol Snyder Kreek 2019 Ji-Sheng Han cannot attend this 50th Anniversary meeting because of a family illness and sends his regards, along with this photo of him with his family.
    [Show full text]
  • Opioid Receptors: Distinct Roles in Mood Disorders Pierre-Eric Lutz, Brigitte Kieffer
    Opioid receptors: distinct roles in mood disorders Pierre-Eric Lutz, Brigitte Kieffer To cite this version: Pierre-Eric Lutz, Brigitte Kieffer. Opioid receptors: distinct roles in mood disorders. Trends in Neurosciences, Elsevier, 2013, 36 (3), pp.195-206. 10.1016/j.tins.2012.11.002. hal-02437989 HAL Id: hal-02437989 https://hal.archives-ouvertes.fr/hal-02437989 Submitted on 14 Jan 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. NIH Public Access Author Manuscript Trends Neurosci. Author manuscript; available in PMC 2014 March 01. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Trends Neurosci. 2013 March ; 36(3): 195–206. doi:10.1016/j.tins.2012.11.002. Opioid receptors: distinct roles in mood disorders Pierre-Eric Lutz and Brigitte L. Kieffer Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de Recherche Scientifique (CNRS)/ Institut National de la Santé et de la Recherche Médicale(INSERM)/ Université de Strasbourg, Illkirch-Graffenstaden, France. Abstract The roles of opioid receptors in pain and addiction have been extensively studied, but their function in mood disorders has received less attention.
    [Show full text]
  • Institute of Genetics & Molecular & Cellular Biology
    2o10 InstItute of GenetIcs & Molecular & cellular BIoloGy contents Foreword 2 Academics 4 Development & Stem Cells 6 Cancer & Functional Genomics 34 Integrated Structural Biology 62 Translational Medicine & Neurogenetics 80 ICS 100 Platforms 102 Core facilities 108 Facts & Figures 110 Staff scientists 112 Prizes & Distinctions 116 Publications until June 2010 117 Publications 2009 120 Where we are 126 Olivier Pourquié, IGBMC Director The IGBMC is one of the leading centers in bio- that are directly interested in biological questions logical research in Europe. It was founded in 1994 with immediate clinical relevance, such as human by Pierre Chambon, one of the world’s leading genetic diseases. figures in biomedical sciences. With its 768 staff One of IGBMC’s major assets are its excellent the Institute represents one of the largest French core facilities and its outstanding technological biomedical research units associating INSERM, platforms, which provide accessible state of the CNRS and the University of Strasbourg. The art technologies to the institute’s scientists. One IGBMC is located close to Strasbourg, a cosmo- of these platforms, the Mouse Clinical Institute politan city hosting the European parliament on (ICS), is rather unusual in that it is a large struc- the frontier between France and Germany. ture employing more than 100 The IGBMC is a highly international center with people exclusively dedicated to 43 Groups 48 different nationalities represented among its mouse technology. Its activities 106 Staff scientists personnel and all activities in the Institute are car- range from transgenic mouse ried out in English. models production to complex 121 Postdoctoral fellows The 43 independent research teams work on a phenotyping strategies inclu- 118 PhD students broad array of topics, ranging from the analysis of ding behavioral and metabolic 37 Master students protein structure to human genetics.
    [Show full text]
  • Mu-Opioid Receptor Knockout Prevents Changes in Delta-Opioid Receptor Trafficking Induced by Chronic Inflammatory Pain
    Pain 109 (2004) 266–273 www.elsevier.com/locate/pain Mu-opioid receptor knockout prevents changes in delta-opioid receptor trafficking induced by chronic inflammatory pain Anne Morinvillea,b,1, Catherine M. Cahilla,2, Brigitte Kiefferc, Brian Collierb, Alain Beaudeta,* aDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, Rm 896, McGill University, 3801 University Street, Montreal, Que., Canada H3A 2B4 bDepartment of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, Que., Canada H3G 1Y6 cIGBMC, CNRS/INSERM/ULP, 67404 Illkirch, France Received 25 July 2003; received in revised form 18 December 2003; accepted 12 January 2004 Abstract Previous studies from our laboratory have demonstrated that both chronic inflammatory pain, induced by intraplantar injection of complete Freund’s adjuvant (CFA), and prolonged (48 h) stimulation of mu-opioid receptors (mOR) by systemic administration of a variety of selective agonists, resulted in enhanced plasma membrane targeting of delta-opioid receptors (dOR) in neurons of the dorsal spinal cord. To determine whether dOR trafficking induced by chronic inflammation was dependent on the activation of mOR, we investigated by immunogold cytochemistry the effects of intraplantar CFA injection on the plasma membrane density of dOR in mOR knockout (KO) mice. In untreated wild-type (WT) mice, only a small proportion of dOR was associated with neuronal plasma membranes in the dorsal horn of the spinal cord. The CFA-induced inflammation produced a significantly higher ratio of plasma membrane to intracellular receptors, as well as a 75% increase in the membrane density of immunoreactive dOR, in dendrites of the ipsilateral dorsal horn as compared to untreated mice.
    [Show full text]
  • Problems of Drug Dependence, 1993: Proceedings of the 55Th Annual Scientific Meeting the College on Problems of Drug Dependence, Inc
    National Institute on Drug Abuse RESEARCH MONOGRAPH SERIES Problems of Drug Dependence, 1993: Proceedings of the 55th Annual Scientific Meeting The College on Problems of Drug Dependence, Inc. Volume I 140 U.S. Department of Health and Human Services • Public Health Service • NATIONAL INSTITUTES OF HEALTH Problems of Drug Dependence, 1993: Proceedings of the 55th Annual Scientific Meeting, The College on Problems of Drug Dependence, Inc. Volume I: Plenary Session Symposia and Annual Reports Editor: Louis S. Harris, Ph.D. NIDA Research Monograph 140 1994 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutes of Health National Institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 ACKNOWLEDGMENT The Committee on Problems of Drug Dependence, Inc., an independent, nonprofit organization, conducts drug testing and evaluations for academic institutions, government, and industry. This monograph is based on papers or presentations from the 55th Annual Scientific Meeting of the CPDD, held in Toronto, Canada, in June 1993. In the interest of rapid dissemination, it is published by the National Institute on Drug Abuse in its Research Monograph series as reviewed and submitted by the CPDD. Dr. Louis S. Harris, editor of this monograph, is Chairman of the Department of Pharmacology, Medical College of Virginia. COPYRIGHT STATUS The National Institute on Drug Abuse has obtained permission from the copyright holders to reproduce certain previously published material as noted in the text. Further reproduction of this copyrighted material is permitted only as part of a reprinting of the entire publication or chapter. For any other use, the copyright holder’s permission is required.
    [Show full text]
  • The Opioid Crisis and the Future of Addiction and Pain Therapeutics S
    Supplemental material to this article can be found at: http://jpet.aspetjournals.org/content/suppl/2019/09/03/jpet.119.259408.DC1 1521-0103/371/2/396–408$35.00 https://doi.org/10.1124/jpet.119.259408 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 371:396–408, November 2019 U.S. Government work not protected by U.S. copyright Special Section on The Opioid Crisis The Opioid Crisis and the Future of Addiction and Pain Therapeutics s Nathan P. Coussens, G. Sitta Sittampalam, Samantha G. Jonson, Matthew D. Hall, Heather E. Gorby, Amir P. Tamiz, Owen B. McManus, Christian C. Felder, and Kurt Rasmussen Downloaded from National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland (N.P.C., G.S.S., S.G.J., M.D.H.); Orvos Communications, LLC (H.E.G.); National Institute of Neurologic Disorders and Stroke (A.P.T.) and National Institute on Drug Abuse (K.R.), National Institutes of Health, Bethesda, Maryland; Q-State Biosciences, Cambridge, Massachusetts (O.B.M.); and VP Discovery Research, Karuna Therapeutics, Boston, Massachusetts (C.C.F.) Received April 23, 2019; accepted August 29, 2019 jpet.aspetjournals.org ABSTRACT Opioid misuse and addiction are a public health crisis resulting in discovery of novel targets and regulatable pain circuits for safe debilitation, deaths, and significant social and economic impact. and effective therapeutics, as well as relevant biomarkers to Curbing this crisis requires collaboration among academic, ensure adequate testing in clinical trials. Applications of improved government, and industrial partners toward the development of technologies including reagents, assays, model systems, and effective nonaddictive pain medications, interventions for opioid validated probe compounds will likely increase the delivery of at ASPET Journals on September 25, 2021 overdose, and addiction treatments.
    [Show full text]
  • Farhana Sarker
    Curriculum Vitae Skype: md.taufiq.nasseef Web: https://sites.google.com/site/tnasseef/home MD. TAUFIQ NASSEEF E-mail: [email protected] Post-doctoral Fellow (January 2016 - present) [email protected] Douglas Brain Imaging Centre [email protected] McGill University Montreal, Canada, Room No E3402, Perry Pavilion, 6875 Boulevard LaSalle, Verdun, QC H4H 1R3, Montreal, Canada Phone: +1-514-862-6907(cell) +1-514-761-6131 ext 4772(office) Address: Apartment no 604, 2055, Saint Mathieu, Montreal, Canada, H3H2J2 Research Interest: • Neurodegenerative Disease • Brain MRI & fMRI • Mathematical Modelling • Brain function & connectivity • Directional connectivity • Computational modelling • Mathematical neuroscience Educat ion: Ph.D. Cognitive and Brain Sciences, Center for Mind and Brain Sciences (CiMeC), University of Trento, Rovereto, Italy, December 2015 [Thesis Title: Measuring directed functional connectivity in mouse fMRI networks using Granger Causality] M. Sc. Mathematics and its applications, School of Mathematics, Statistics and Actuarial Science University of Kent, Canterbury Campus, UK, October 2012 [Dissertation Topic: Counting Symmetries] M. Sc. Mathematics, Jahangirnagar University (JU), Savar, Dhaka, Bangladesh, 1st Class, April 2007. [Thesis Title: A study of solvable groups] B. Sc. Mathematics, Jahangirnagar University (JU), Savar,Dhaka, Bangladesh, 1st Class, March 2005. Research outcomes: Peer Reviewed Journals (Neuroscience): • Md Taufiq Nasseef, Jai Puneet Singh, Aliza T. Ehrlich, Michael McNicholas,
    [Show full text]
  • Mu Opioid Receptors and Neuronal Circuits of Addiction: Genetic Approaches in Mice
    UNIVERSITÉ DE STRASBOURG École Doctorale des Sciences de la Vie et de la Santé IGBMC - CNRS UMR 7104 - Inserm U 964 THÈSE présentée par : Pauline CHARBOGNE soutenue le : 9 juillet 2015 pour obtenir le grade de : Docteur de l’université de Strasbourg en Aspects Moléculaires et Cellulaires de la Biologie Mention Neurosciences Mu opioid receptors and neuronal circuits of addiction: genetic approaches in mice THÈSE dirigée par : Mme KIEFFER Brigitte L. Professeure, Université de Strasbourg/McGill University RAPPORTEURS : M. BELIN David Maître de conférences, University of Cambridge Mme LE MOINE Catherine Directrice de recherche, Université de Bordeaux M. ZWILLER Jean Directeur de recherche, Université de Strasbourg RVIV`H1VIVJ s V" 1VJ&";"R1`V"%J"$`:JR"IV`H1":%"]`Q`V&&V%`"2`1$1 V"31V``V`5"]Q%`"I;:0Q1`":HH%V1CC1V"R:J&"&QJ"X_%1]V"V " $%1RXV R:Js IQJ `:0:1C RV .WsV8 MV`H1 ]Q%` Q% Vs CVs R1sH%ss1QJs RV `QJR _%1" I;QJ " :IVJXV" ;" RX0VCQ]]V` %J `V$:`R H`1 1_%V V HQJs `%H 1` s%` IVs ]`Q=V s8 MV`H1 ]Q%` Q% CV VI]s _%V"0Q%&"I;:0V< HQJ&:H`X5" =V" &:1&" _%;1C" V& " ]`XH1V%68 J $`:JR IV`H1 X$:CVIVJ ]Q%` 0Q `V `:JsI1ss1QJ R% $Q( RV C;XH`1 %`V ^H;X :1 ":&&V<"1J: VJR% *_8 JV 1VJs ; `VIV`H1V` CVs RQH V%`s D:01R BVC1J5 C: .V`1JV LV MQ1JV5 JV:J 11CCV`5 AGRVC O%:$:<<:C V K: 1: 2V`Q` "R;:0Q1`":HHV] X"R;X0:C%V`"IQJ" `:0:1C 8 MV`H1 ; Q%s CVs B`1@1 V:I IVIGV`s s `:sGQ%`$VQ1s ]:ssXs V ]`XsVJ s5 C:`Q5 SV`H:J5 :05 D:01R5 HV`0X5 L:%`1VRAJJV5 CC:1`V5 R:].5 C.1.1`Q5 AGRVC5 P:sH:CV5 P1V``VRE`1H5 0:J5 AC1HV5 C:`QCV5 JX`TIV5 J%C1V5 AC1JV5 M1H.VC5 P:%C5 L:%`VJHV5 MV$:J
    [Show full text]