DOCSLIB.ORG

Treatment of Problem Cocaine Use a Review of the Literature the of Review a Literature

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Treatment of Problem Cocaine Use a Review of the Literature the of Review a Literature TREATMENT OF PROBLEM COCAINE USE COCAINE PROBLEM OF TREATMENT A REVIEW OF THE LITERATURE LITERATURE REVIEW ISBN 92-9168-274-8 ISBN EMCDDA literature reviews Treatment of problem cocaine use: a review of the literature EMCDDA literature reviews — Treatment of problem cocaine use Acknowledgements This literature review is based on a consultant report by Christian Haasen and Katja Thane, Institut für Interdisziplinäre Sucht- und Drogenforschung (ISD), Hamburg, at the Zentrum für Interdisziplinäre Suchtforschung (ZIS) of the University of Hamburg (Service Contract CT.06.RES.144.1.0). EMCDDA project managers: Dagmar Hedrich and Alessandro Pirona. Other contributors to this project included Prepress Projects, Rosemary de Sousa and Peter Thomas. Cataloguing data European Monitoring Centre for Drugs and Drug Addiction, 2007 EMCDDA Literature reviews — Treatment of problem cocaine use: a review of the literature Lisbon: European Monitoring Centre for Drugs and Drug Addiction 2007 — 50 pp. — 21 x 29.7 cm Language: EN Catalogue Number: TD-XB-06-001-EN-N ISBN: 92-9168-274-8 ISSN: 1725-0579 © European Monitoring Centre for Drugs and Drug Addiction, 2007. Reproduction is authorised provided the source is acknowledged. Rua da Cruz de Santa Apolónia 23-25, PT-1149-045 Lisbon, Portugal Tel: (+351) 21 811 3000 Fax: (+351) 21 813 1711 [email protected] http://www.emcdda.europa.eu 3 EMCDDA literature reviews — Treatment of problem cocaine use List of abbreviations ADHD attention deficit hyperactivity disorder BBD blood-borne disease CA Cocaine Anonymous CBT cognitive–behavioural therapy CEDRO Centrum voor Drugsonderzoek (Netherlands) CM contingency management CNS central nervous system CRA community reinforcement approach CRH corticotrophin-releasing hormone DA dopamine DSM-IV Diagnostic and Statistical Manual of Mental Disorder (4th edition) EMCDDA European Monitoring Centre for Drugs and Drug Addiction FOS Forschungsverbund stationäre Suchttherapie (Switzerland) GABA gamma-aminobutyric acid GP general practitioner GVG gamma-vinyl-GABA HIV human immunodeficiency virus IDU injecting drug user IFT Institut für Therapieforschung (Munich, Germany) ISD Instituut voor Sociaal Drugonderzoek (Belgium) MAO monoamine oxidase MI motivational interviewing MMT methadone maintenance treatment NADA National Acupuncture Detoxification Association NcA nucleus accumbens NHS National Health Service (UK) NIDA National Institute on Drugs and Drug Abuse (USA) NSAID non-steroidal anti-inflammatory drug NTA National Treatment Agency (UK) NTORS National Treatment Outcome Research Study (UK) RCT randomised controlled trial Reitox European Information Network on Drugs and Drug Addiction SROM slow-release oral morphine SSRI selective serotonin reuptake inhibitor TC therapeutic community TCA 2,4,6-trichloranisol Trimbos Netherlands Institute Of Mental Health And Addiction WHO World Health Organization 4 EMCDDA literature reviews — Treatment of problem cocaine use Table Of Contents List of abbreviations ............................................................................................................................. 4 Table Of Contents.................................................................................................................................. 5 Foreword ................................................................................................................................................ 6 1 History and epidemiological characteristics of cocaine use .................................7 2 Current issues in the treatment of problem cocaine use .......................................9 2.1 Research and evaluation ................................................................................................... 9 2.2 Polydrug use and heterogeneity of client profiles.............................................................. 9 2.3 Treatment entry................................................................................................................ 10 2.4 Quality assurance ............................................................................................................ 10 3 Pharmacological treatment .....................................................................................13 3.1 Substances for relapse prevention .................................................................................. 13 3.2 Other pharmacological measures.................................................................................... 19 3.3 Immunisation and vaccination ......................................................................................... 19 3.4 Optimising opioid treatment in the presence of additional cocaine use .......................... 20 3.5 Treatment of cocaine use in subjects with other psychiatric disorders ........................... 21 4 Psychosocial treatment ...........................................................................................24 4.1 Cognitive–behavioural therapy (CBT) and other behavioural approaches ..................... 24 4.2 Rewards/punishment-based therapies ............................................................................ 26 4.3 Motivational interviewing.................................................................................................. 27 4.4 Relapse prevention.......................................................................................................... 28 4.5 Family therapy ................................................................................................................. 29 4.6 Counselling ...................................................................................................................... 29 4.7 Other approaches ............................................................................................................ 29 5 Harm reduction .........................................................................................................31 6 Inpatient treatment ...................................................................................................33 7 Aftercare....................................................................................................................34 8 Conclusion ................................................................................................................35 Bibliography......................................................................................................................................... 36 5 EMCDDA literature reviews — Treatment of problem cocaine use Foreword Treatment systems in Europe are increasingly confronted with cocaine use-related problems. After opioids and cannabis, cocaine has become the third most commonly reported reason for entering drug treatment and accounted for about 8 % of all treatment demands across the EU in 2004. This overall figure reflects a wide variation between countries; however, the proportion of new clients demanding treatment for cocaine use is estimated to have grown from 10 % to 20 % during the period 1999–2004 (EMCDDA, 2006). Cocaine use has also become more common among drug users in contact with outreach workers or low-threshold agencies, and new findings with respect to treatment need to be evaluated in order to adapt addiction services to the new demands. The aim of this report is to provide an up-to-date summary of research regarding treatment approaches to cocaine dependency, and their effectiveness1. New treatment concepts need to be evidence based, calling for a research perspective in the evaluation of treatments for cocaine dependence. Nonetheless, innovations in treatment also result from individual experiments by clinicians, so that a clinical perspective needs to be added in order to obtain a complete overview of developments in the treatment of cocaine dependence. In this direction, conferences were organized across Europe to gather further knowledge on cocaine treatment by bringing together European researchers and clinicians. For example, a conference on clinical research on cocaine took place in April 2006 in Paris organised by the Mission Interministérielle de Lutte contre la Drogue et la Toxicomanie. In June 2006, the Federazione Italiana Comunità Terapeutiche (FICT) organised in Rome the Congress ‘Cocaina: la FICT tra prassi e innovazione: Esperienze a confronto nel contesto italiano’ with the aim of sharing experiences and disseminating best practices in relation to cocaine treatment. A similar conference was held in Madrid on the 17th of May 2007. In conclusion, the present report aims to portray the state-of-the-art in health responses to cocaine use, with a special emphasis on mental health problems related to cocaine use. However, there is no doubt that current research efforts will in the near future bring about innovations of great importance in this field. We hope that this report will support the dynamic research process that is under way and at the same time support adjustments in policy regarding addiction services to improve their response to cocaine users. (1) This report reviews the current literature on cocaine treatment, based on a search of the databases Medline, PubMed and PsychInfo for the years 2002–07, using the following keywords: cocaine, treatment, dependence. In addition, the reference lists of all publications identified through the search were evaluated and reports from European research centres, including Trimbos and Cedro in the Netherlands, ISD in Belgium, IFT in Germany and the NTA in the UK, were also considered. Please note
Load more

Recommended publications
  • Experimental Dopamine Reuptake Inhibitors in Parkinson’S Disease: a Review of the Evidence
    Journal of Experimental Pharmacology Dovepress open access to scientific and medical research Open Access Full Text Article REVIEW Experimental Dopamine Reuptake Inhibitors in Parkinson’s Disease: A Review of the Evidence This article was published in the following Dove Press journal: Journal of Experimental Pharmacology Thomas Müller Abstract: Parkinson’s disease (PD) is the second most chronic neurodegenerative disorder worldwide. Deficit of monoamines, particularly dopamine, causes an individually varying Department of Neurology, St. Joseph Hospital Berlin-Weissensee, Berlin, compilation of motor and non-motor features. Constraint of presynaptic uptake extends 13088, Germany monoamine stay in the synaptic cleft. This review discusses possible benefits of dopamine reuptake inhibition for the treatment of PD. Translation of this pharmacologic principle into positive clinical study results failed to date. Past clinical trial designs did not consider a mandatory, concomitant stable inhibition of glial monoamine turnover, i.e. with mono­ amine oxidase B inhibitors. These studies focused on improvement of motor behavior and levodopa associated motor complications, which are fluctuations of motor and non-motor behavior. Future clinical investigations in early, levodopa- and dopamine agonist naïve patients shall also aim on alleviation of non-motor symptoms, like fatigue, apathy or cognitive slowing. Oral levodopa/dopa decarboxylase inhibitor application is inevitably necessary with advance of PD. Monoamine reuptake (MRT) inhibition improves the efficacy of levodopa, the blood brain barrier crossing metabolic precursor of dopamine. The pulsatile brain delivery pattern of orally administered levodopa containing formulations results in synaptic dopamine variability. Ups and downs of dopamine counteract the physiologic principle of continuous neurotransmission, particularly in nigrostriatal, respectively meso­ corticolimbic pathways, both of which regulate motor respectively non-motor behavior.
    [Show full text]
  • WO 2017/145013 Al 31 August 2017 (31.08.2017) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2017/145013 Al 31 August 2017 (31.08.2017) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07D 498/04 (2006.01) A61K 31/5365 (2006.01) kind of national protection available): AE, AG, AL, AM, C07D 519/00 (2006.01) A61P 25/00 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, (21) Number: International Application DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/IB20 17/050844 HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, (22) International Filing Date: KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, 15 February 2017 (15.02.2017) MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, (25) Filing Language: English RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, (26) Publication Language: English TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 62/298,657 23 February 2016 (23.02.2016) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant: PFIZER INC. [US/US]; 235 East 42nd Street, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, New York, New York 10017 (US).
    [Show full text]
  • Addictions and the Brain
    9/18/2012 Addictions and the Brain TAAP Conference September 14, 2012 Acknowledgements • La Hacienda Treatment Center • American Society of Addiction Medicine • National Institute of Drug Abuse © 2012 La Hacienda Treatment Center. All rights reserved. 1 9/18/2012 Definition • A primary, progressive biochemical, psychosocial, genetically transmitted chronic disease of relapse who’s hallmarks are denial, loss of control and unmanageability. DSM IV Criteria for dependency: At least 3 of the 7 below 1. Withdrawal 2. Tolerance 3. The substance is taken in larger amounts or over a longer period than was intended. 4. There is a persistent desire or unsuccessful efforts to cut down or control substance use. 5. A great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover from its effects. 6. Important social, occupational, or recreational activities are given up or reduced because of the substance use. 7. The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance. © 2012 La Hacienda Treatment Center. All rights reserved. 2 9/18/2012 Dispute between behavior and disease Present understanding of the Hypothalamus location of the disease hypothesis. © 2012 La Hacienda Treatment Center. All rights reserved. 3 9/18/2012 © 2012 La Hacienda Treatment Center. All rights reserved. 4 9/18/2012 © 2012 La Hacienda Treatment Center. All rights reserved. 5 9/18/2012 Dispute regarding behavior versus disease © 2012 La Hacienda Treatment Center. All rights reserved. 6 9/18/2012 © 2012 La Hacienda Treatment Center.
    [Show full text]
  • Upregulation of Peroxisome Proliferator-Activated Receptor-Α And
    Upregulation of peroxisome proliferator-activated receptor-α and the lipid metabolism pathway promotes carcinogenesis of ampullary cancer Chih-Yang Wang, Ying-Jui Chao, Yi-Ling Chen, Tzu-Wen Wang, Nam Nhut Phan, Hui-Ping Hsu, Yan-Shen Shan, Ming-Derg Lai 1 Supplementary Table 1. Demographics and clinical outcomes of five patients with ampullary cancer Time of Tumor Time to Age Differentia survival/ Sex Staging size Morphology Recurrence recurrence Condition (years) tion expired (cm) (months) (months) T2N0, 51 F 211 Polypoid Unknown No -- Survived 193 stage Ib T2N0, 2.41.5 58 F Mixed Good Yes 14 Expired 17 stage Ib 0.6 T3N0, 4.53.5 68 M Polypoid Good No -- Survived 162 stage IIA 1.2 T3N0, 66 M 110.8 Ulcerative Good Yes 64 Expired 227 stage IIA T3N0, 60 M 21.81 Mixed Moderate Yes 5.6 Expired 16.7 stage IIA 2 Supplementary Table 2. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of an ampullary cancer microarray using the Database for Annotation, Visualization and Integrated Discovery (DAVID). This table contains only pathways with p values that ranged 0.0001~0.05. KEGG Pathway p value Genes Pentose and 1.50E-04 UGT1A6, CRYL1, UGT1A8, AKR1B1, UGT2B11, UGT2A3, glucuronate UGT2B10, UGT2B7, XYLB interconversions Drug metabolism 1.63E-04 CYP3A4, XDH, UGT1A6, CYP3A5, CES2, CYP3A7, UGT1A8, NAT2, UGT2B11, DPYD, UGT2A3, UGT2B10, UGT2B7 Maturity-onset 2.43E-04 HNF1A, HNF4A, SLC2A2, PKLR, NEUROD1, HNF4G, diabetes of the PDX1, NR5A2, NKX2-2 young Starch and sucrose 6.03E-04 GBA3, UGT1A6, G6PC, UGT1A8, ENPP3, MGAM, SI, metabolism
    [Show full text]
  • Metabolism and Pharmacokinetics in the Development of New Therapeutics for Cocaine and Opioid Abuse
    University of Mississippi eGrove Electronic Theses and Dissertations Graduate School 2012 Metabolism And Pharmacokinetics In The Development Of New Therapeutics For Cocaine And Opioid Abuse Pradeep Kumar Vuppala University of Mississippi Follow this and additional works at: https://egrove.olemiss.edu/etd Part of the Pharmacy and Pharmaceutical Sciences Commons Recommended Citation Vuppala, Pradeep Kumar, "Metabolism And Pharmacokinetics In The Development Of New Therapeutics For Cocaine And Opioid Abuse" (2012). Electronic Theses and Dissertations. 731. https://egrove.olemiss.edu/etd/731 This Dissertation is brought to you for free and open access by the Graduate School at eGrove. It has been accepted for inclusion in Electronic Theses and Dissertations by an authorized administrator of eGrove. For more information, please contact [email protected]. METABOLISM AND PHARMACOKINETICS IN THE DEVELOPMENT OF NEW THERAPEUTICS FOR COCAINE AND OPIOID ABUSE A Dissertation presented in partial fulfillment of requirements for the degree of Doctor of Philosophy in Pharmaceutical Sciences in the Department of Pharmaceutics The University of Mississippi by PRADEEP KUMAR VUPPALA April 2012 Copyright © 2012 by Pradeep Kumar Vuppala All rights reserved ABSTRACT Cocaine and opioid abuse are a major public health concern and the cause of significant morbidity and mortality worldwide. The development of effective medication for cocaine and opioid abuse is necessary to reduce the impact of this issue upon the individual and society. The pharmacologic treatment for drug abuse has been based on one of the following strategies: agonist substitution, antagonist treatment, or symptomatic treatment. This dissertation is focused on the role of metabolism and pharmacokinetics in the development of new pharmacotherapies, CM304 (sigma-1 receptor antagonist), mitragynine and 7-hydroxymitragynine (µ-opioid receptor agonists), for the treatment of drug abuse.
    [Show full text]
  • Medications and Alcohol Craving
    Medications and Alcohol Craving Robert M. Swift, M.D., Ph.D. The use of medications as an adjunct to alcoholism treatment is based on the premise that craving and other manifestations of alcoholism are mediated by neurobiological mechanisms. Three of the four medications approved in the United States or Europe for treating alcoholism are reported to reduce craving; these include naltrexone (ReVia™), acamprosate, and tiapride. The remaining medication, disulfiram (Antabuse®), may also possess some anticraving activity. Additional medications that have been investigated include ritanserin, which has not been shown to decrease craving or drinking levels in humans, and ondansetron, which shows promise for treating early onset alcoholics, who generally respond poorly to psychosocial treatment alone. Use of anticraving medications in combination (e.g., naltrexone plus acamprosate) may enhance their effectiveness. Future studies should address such issues as optimal dosing regimens and the development of strategies to enhance patient compliance. KEY WORDS: AOD (alcohol and other drug) craving; anti alcohol craving agents; alcohol withdrawal agents; drug therapy; neurobiological theory; alcohol cue; disulfiram; naltrexone; calcium acetylhomotaurinate; dopamine; serotonin uptake inhibitors; buspirone; treatment outcome; reinforcement; neurotransmitters; patient assessment; literature review riteria for defining alcoholism Results of craving research are often tions (i.e., pharmacotherapy) to improve vary widely. Most definitions difficult to interpret,
    [Show full text]
  • A Role for Histone Modification in the Mechanism of Action of Antidepressant and Stimulant Drugs: a Dissertation
    University of Massachusetts Medical School eScholarship@UMMS GSBS Dissertations and Theses Graduate School of Biomedical Sciences 2007-12-28 A Role for Histone Modification in the Mechanism of Action of Antidepressant and Stimulant Drugs: a Dissertation Frederick Albert Schroeder University of Massachusetts Medical School Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/gsbs_diss Part of the Amino Acids, Peptides, and Proteins Commons, Cells Commons, Enzymes and Coenzymes Commons, Genetic Phenomena Commons, Mental Disorders Commons, Nervous System Commons, and the Therapeutics Commons Repository Citation Schroeder FA. (2007). A Role for Histone Modification in the Mechanism of Action of Antidepressant and Stimulant Drugs: a Dissertation. GSBS Dissertations and Theses. https://doi.org/10.13028/7bk0-a687. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/370 This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in GSBS Dissertations and Theses by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. A Dissertation Presented by Frederick Albert Schroeder Submitted to the Faculty of the University of Massachusetts Graduate School of Biomedical Sciences Worcester, Massachusetts, USA in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY December 28, 2007 Program in Neuroscience A Role for Histone Modification in the Mechanism of Action of Antidepressant and Stimulant Drugs A Dissertation Presented By Frederick Albert Schroeder Approved as to style and content by: _____________________________________ Alonzo Ross, Ph.D., Chair of Committee _____________________________________ Pradeep Bhide, Ph.D., Member of Committee _____________________________________ Craig L.
    [Show full text]
  • Alcohol-Medication Interactions: the Acetaldehyde Syndrome
    arm Ph ac f ov l o i a g n il r a n u c o e J Journal of Pharmacovigilance Borja-Oliveira, J Pharmacovigilance 2014, 2:5 ISSN: 2329-6887 DOI: 10.4172/2329-6887.1000145 Review Article Open Access Alcohol-Medication Interactions: The Acetaldehyde Syndrome Caroline R Borja-Oliveira* University of São Paulo, School of Arts, Sciences and Humanities, São Paulo 03828-000, Brazil *Corresponding author: Caroline R Borja-Oliveira, University of São Paulo, School of Arts, Sciences and Humanities, Av. Arlindo Bettio, 1000, Ermelino Matarazzo, São Paulo 03828-000, Brazil, Tel: +55-11-30911027; E-mail: [email protected] Received date: August 21, 2014, Accepted date: September 11, 2014, Published date: September 20, 2014 Copyright: © 2014 Borja-Oliveira CR. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Medications that inhibit aldehyde dehydrogenase when coadministered with alcohol produce accumulation of acetaldehyde. Acetaldehyde toxic effects are characterized by facial flushing, nausea, vomiting, tachycardia and hypotension, symptoms known as acetaldehyde syndrome, disulfiram-like reactions or antabuse effects. Severe and even fatal outcomes are reported. Besides the aversive drugs used in alcohol dependence disulfiram and cyanamide (carbimide), several other pharmaceutical agents are known to produce alcohol intolerance, such as certain anti-infectives, as cephalosporins, nitroimidazoles and furazolidone, dermatological preparations, as tacrolimus and pimecrolimus, as well as chlorpropamide and nilutamide. The reactions are also observed in some individuals after the simultaneous use of products containing alcohol and disulfiram-like reactions inducers.
    [Show full text]
  • AN OPEN RANDOMIZED STUDY COMPARING DISULFIRAM and ACAMPROSATE in the TREATMENT of ALCOHOL DEPENDENCE AVINASH DE SOUSA* and ALAN DE SOUSA
    Alcohol & Alcoholism Vol. 40, No. 6, pp. 545–548, 2005 doi:10.1093/alcalc/agh187 Advance Access publication 25 July 2005 AN OPEN RANDOMIZED STUDY COMPARING DISULFIRAM AND ACAMPROSATE IN THE TREATMENT OF ALCOHOL DEPENDENCE AVINASH DE SOUSA* and ALAN DE SOUSA Get Well Clinic And Nursing Home, 33rd Road, Off Linking Road, Bandra, Mumbai 400050, Maharashtra State, India (Received 11 March 2005; first review notified 6 June 2005; in final revised form 21 June 2005; accepted 2 July 2005; advance access publication 25 July 2005) Abstract — Aims: To compare the efficacy of acamprosate (ACP) and disulfiram (DSF) for preventing alcoholic relapse in routine clinical practice. Methods: One hundred alcoholic men with family members who would encourage medication compliance and accom- pany them for follow-up were randomly allocated to 8 months of treatment with DSF or ACP. Weekly group psychotherapy was also available. The psychiatrist, patient, and family member were aware of the treatment prescribed. Alcohol consumption, craving, and adverse events were recorded weekly for 3 months and then fortnightly. Serum gamma glutamyl transferase was measured at the start Downloaded from https://academic.oup.com/alcalc/article/40/6/545/125907 by guest on 27 September 2021 and the end of the study. Results: At the end of the trial, 93 patients were still in contact. Relapse (the consumption of >5 drinks/40 g of alcohol) occurred at a mean of 123 days with DSF compared to 71 days with ACP (P = 0.0001). Eighty-eight per cent of patients on DSF remained abstinent compared to 46% with ACP (P = 0.0002).
    [Show full text]
  • Characterization of Mice with Altered Dopamine Transporter and Vesicular Monoamine Transporter 2 Levels
    Characterization of Mice with Altered Dopamine Transporter and Vesicular Monoamine Transporter 2 Levels by Shababa Tanzeel Masoud A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Pharmacology and Toxicology University of Toronto © Copyright by Shababa Tanzeel Masoud 2017 Characterization of Mice with Altered Dopamine Transporter and Vesicular Monoamine Transporter 2 Levels Shababa Tanzeel Masoud Doctor of Philosophy Department of Pharmacology and Toxicology University of Toronto 2017 Abstract Dopamine is a key neurotransmitter that regulates motor coordination and dysfunction of the dopamine system gives rise to Parkinson’s disease. Nigrostriatal dopamine neurons are vulnerable to various genetic and environmental insults, suggesting that these cells are inherently at-risk. A cell-specific risk factor for these neurons is the neurotransmitter, dopamine itself. If intracellular dopamine is not appropriately sequestered into vesicles, it can accumulate in the cytosol. Cytosolic dopamine is highly reactive and can trigger oxidative stress, leading to cellular toxicity. Cytosolic dopamine levels are modulated by the plasma membrane dopamine transporter (DAT) that takes up dopamine from the extracellular space, and the vesicular monoamine transporter 2 (VMAT2) that stores dopamine into vesicles. In this thesis, we altered DAT and VMAT2 levels to investigate the detrimental consequences of potentially amplifying cytosolic dopamine in transgenic mice. Project 1 focused on selective over-expression of DAT in dopaminergic cells of transgenic mice (DAT-tg). DAT-tg mice displayed phenotypes of dopaminergic damage: increased dopamine-specific oxidative stress, L-DOPA-reversible fine motor deficits and enhanced sensitivity to toxicant insult, suggesting that increasing DAT- mediated dopamine uptake is detrimental for dopamine cells.
    [Show full text]
  • Lega Italiana Per La Lotta Contro La Malattia Di Parkinson Le Sindromi Extrapiramidali E Le Demenze
    LIMPE lega italiana per la lotta contro la malattia di parkinson le sindromi extrapiramidali e le demenze Web site: http://www.parkinson-limpe.it/ XXIX National Congress Lecce 23–25 October 2002 Parkinson Parkinsonism Dementia: from Biotechnology to Medical Management SELECTED SHORT PAPERS Scientific Committee Bruno Bergamasco, Giovanni U. Corsini, Mario Manfredi, Stefano Ruggieri, Pierfranco Spano Secretariat LIMPE Viale dell’Università 30, 00185 Roma Tel. and Fax: +39-06-4455618 E-mail: [email protected] Neurol Sci (2003) 24:149–150 DOI 10.1007/s10072-003-0103-5 123I-Ioflupane/SPECT binding to to the dopamine transporter (DAT) may be better suited and provide more-accurate estimation of degeneration. Several striatal dopamine transporter (DAT) tracers that bind to DAT and utilize SPECT are available; uptake in patients with Parkinson’s they are all cocaine derivatives. The most widely used are disease, multiple system atrophy, and [123I]β-CIT and 123I-Ioflupane ([123I]FP-CIT) [3, 4]. The main advantage of 123I-Ioflupane is that a steady state allow- progressive supranuclear palsy ing SPECT imaging is reached 3 h after a single bolus injec- 1 2 1 tion of the radioligand, compared with the 18–24 h required A. Antonini (౧) • R. Benti • R. De Notaris 1 1 1 for [123I]β-CIT. Therefore DAT imaging with 123I-Ioflupane S. Tesei • A. Zecchinelli • G. Sacilotto 1 1 1 1 can be completed the same day. N. Meucci • M. Canesi • C. Mariani • G. Pezzoli 123 P. Gerundini2 Several studies have demonstrated the usefulness of I- 1 Centro per la malattia di Parkinson, Dipartimento di Ioflupane SPECT imaging in the diagnosis of parkinsonism.
    [Show full text]
  • Selective Knockdown of TASK3 Potassium Channel in Monoamine
    Manuscript Click here to download Manuscript Fullana et al - TASK3.docx 1 Research Article – Molecular Neurobiology 2 3 Selective Knockdown of TASK3 Potassium Channel in Monoamine 4 Neurons: A New Therapeutic Approach for Depression 5 M Neus Fullana1,2,3*, Albert Ferrés-Coy1,2,3*, Jorge E Ortega3,4, Esther Ruiz-Bronchal1,2,3, Verónica 6 Paz1,2,3, J Javier Meana3,4, Francesc Artigas1,2,3 and Analia Bortolozzi1,2,3 7 8 1Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain 9 2Department of Neurochemistry and Neuropharmacology, IIBB-CSIC (Consejo Superior de 10 Investigaciones Científicas), Barcelona, Spain. 11 3Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), ISCIII, Madrid, Spain. 12 4Department of Pharmacology, University of Basque Country UPV/EHU and BioCruces Health 13 Research Institute, Bizkaia, Spain 14 15 NF* and AF-C* contributed equally to this work. 16 For correspondence: Analia Bortolozzi, Department of Neurochemistry and Neuropharmacology 17 (IIBB-CSIC), Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Rosello 161, 18 Barcelona 08036, Spain. Tel: +34 93638313 Fax: +34 933638301 E-mail: 19 [email protected] 20 21 22 23 Running title: Intranasal delivery of conjugated TASK3-siRNA 24 25 26 1 Abstract 2 Current pharmacological treatments for major depressive disorder (MDD) are severely compromised 3 by both slow action and limited efficacy. RNAi strategies have been used to evoke antidepressant-like 4 effects faster than classical drugs. Using small interfering RNA (siRNA), we herein show that TASK3 5 potassium channel knockdown in monoamine neurons induces antidepressant-like responses in mice.
    [Show full text]