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In this Section
- Office of the Scientific Director
- Office of the Clinical Director
- NIAAA Laboratories
- Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology (CPN)
- Laboratory of Behavioral & Genomic Neuroscience
- Laboratory of Clinical & Translational Studies
- Laboratory for Integrative Neuroscience
- LIN - Office of the Chief
- LIN - Section on Neuronal Structure
- LIN - Section of Synaptic Pharmacology (SP)
- Laboratory of Liver Diseases
- Laboratory of Membrane Biochemistry and Biophysics
- Laboratory of Metabolic Control
- Laboratory of Molecular Physiology
- Laboratory of Molecular Signaling
- Laboratory of Neurogenetics
- Laboratory for Neuroimaging
- Laboratory of Physiologic Studies
- Chemical Biology Research Branch (joint lab with NIDA)
- Office of Laboratory Animal Science (OLAS)
- Research and Training
- Clinical Trials at NIAAA/NIH
LCTS - Section of Molecular Pathophysiology (MP)
Section of Molecular Pathophysiology, LCTS
National Institute on Alcohol Abuse and Alcoholism
National Institutes of Health
10 Center Drive, Room 10-CRC/1E-5334: MSC 1108
Bethesda MD 20892-1108
What we do
The MP section was created in 2004. We do the basic science that is aimed at discovering novel molecular targets for treatment of alcoholism. Once identified, these can feed into early human studies carried out by other components of the LCTS. The MP section focuses on long-term neuroadaptations in the central nervous system, and on stress-systems that mediate negative affective states in addiction. Although initial drug use is driven by rewarding drug effects, over time drugs lose their reward value. Instead negative affect and increased sensitivity to stress are experienced in the absence of drug, and compulsive drug use is maintained by relief of negative affect.
Our discovery work typically starts out with rodent models of alcoholism and related behaviors, such as anxiety and stress responses. We use rat and mouse paradigms to model excessive voluntary alcohol intake and relapse to alcohol seeking triggered by stress. Various methods, such as e.g. Whole Transcriptome Sequencing, Nanostring, and Affymetrix Gene and SNP microarrays, are used to screen for differential gene expression within brain areas important for negative emotions and stress, in order to discover candidate treatment targets. These are confirmed through quantitative expression analysis and anatomical mapping using in situ hybridization, Real-Time PCR, protein analyses, receptor binding or receptor signaling analysis. The functional role of confirmed candidate targets is finally examined by going back to the animal models, and using pharmacological or molecular approaches to determine whether blocking or otherwise interfering with a confirmed candidate target will reduced excessive alcohol intake, or relapse-like behavior.
Jenica Tapocik, PhD
The primary objective of my research is to understand the neurobiological mechanisms that underlie alcohol dependence with an emphasis on the role of gene networks and microRNAs (miRNAs) in these processes. I use a multidisciplinary strategy including behavioral paradigms, physiological analyses, molecular biological and neurochemical techniques, and bioinformatic analyses to address my research hypotheses. Recent projects consist of whole transcriptome, small RNA, and methylome sequencing, viral-vector based gene and miRNA in vivo manipulation, and in vitro miRNA confirmation and manipulation in cell culture and primary neuron cultures.
Erick Singley is a chemist and runs our analytical core, which involves everything from measuring blood alcohol levels in humans as well as experimental animals, through HPLC analyses of monoamines and their metabolites in cerebrospinal fluid, to analyses of neuropeptides using immune-based methods. In addition, he is responsible for the maintenance of equipment, including property management and the procurement of equipment and supplies for LCTS.
Hui Sun, MD
Dr. Sun runs a range of molecular methods in the laboratory, ranging from genotyping of human research subjects, non-human primate variants and mutant mice, through expression analysis using Real-Time PCR, reporter assays and other methods, to functional analysis such as expression of neurotransmitter receptor variants.
Robert Eskay, PhD
Dr. Eskay studies biochemical and neurotransmitter systems involved in alcohol-induced neurotoxicity, as well as neuroprotective mechanisms. He also has a long standing interest in brain neuropeptide systems and their role in alcohol-related mechanisms. In a collaboration with the NIHGR Center for Chemical Genomics, he is currently involved in efforts to develop ligands for a novel neuropeptide receptor that would enable our lab to evaluate this receptor as a candidate treatment target.
Ruslan Damadzic, MD
Dr. Damadzic works with the research team to better understand the consequences of excessive ethanol consumption on the brain, studies of stress, and alcoholism and alcohol related behaviors. His research efforts are focused on understanding the brain’s biological changes that lead to excessive alcohol consumption and the neurochemical changes that occur with alcohol dependence.
Estelle Barbier, PhD
Dr. Barbier joined LCTS in September 2008. She previously obtained her PhD in Neuroscience in a research group focusing on alcohol and dependence to drugs, the "Groupe de Recherche sur l’Alcool et les Pharmacodépendances" at Picardie Jules Verne University (France). Dr. Barbier currently studies the potential effect of ethanol exposure on DNA methylation and acetylation using a "post dependent" rat model.
Jesse Schank, PhD
Dr. Schank’s work explores the role of neuropeptides in alcohol dependence and alcohol seeking behavior. Specific systems that are assessed include substance P/NK1 and endogenous opioids. Using preclinical animal models, he studies the way in which these systems influence the expression of behaviors induced by alcohol dependence, with the ultimate goal of contributing to the development of novel pharmacotherapies for alcoholism. To further explore the specific mechanisms involved in these treatments, Dr. Schank plans to study the interaction of these systems with monoamine neurotransmitters and neuropeptides involved in stress responses, such as CRH.
Eric Augier, PhD
Alexandra Pincus, BS
Faaz Rehman, BS
Schank JR, Tapocik JD, Barbier E, Damadzic R, Eskay RL, Sun H, Rowe KE, King CE, Yao M, Flanigan ME, Solomon MG, Karlsson C, Cheng K, Rice KC, Heilig M (2013) Tacr1 Gene Variation and Neurokinin 1 Receptor Expression Is Associated with Antagonist Efficacy in Genetically Selected Alcohol-Preferring Rats. Biological psychiatry, e-pub.
Barbier E, Vendruscolo LF, Schlosburg JE, Edwards S, Juergens N, Park PE, Misra KK, Cheng K, Rice KC, Schank J, Schulteis G, Koob GF, Heilig M (2012) The NK1 Receptor Antagonist L822429 Reduces Heroin Reinforcement. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, e-pub.
Barr CS, Chen SA, Schwandt ML, Lindell SG, Sun H, Suomi SJ, Heilig M (2010) Suppression of alcohol preference by naltrexone in the rhesus macaque: a critical role of genetic variation at the micro-opioid receptor gene locus. Biological psychiatry 67:78-80.
Barr CS, Schwandt ML, Lindell SG, Higley JD, Maestripieri D, Goldman D, Suomi SJ, Heilig M (2008) Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates. Proceedings of the National Academy of Sciences of the United States of America 105:5277-5281.
Barr CS, Dvoskin RL, Gupte M, Sommer W, Sun H, Schwandt ML, Lindell SG, Kasckow JW, Suomi SJ, Goldman D, Higley JD, Heilig M (2009) Functional CRH variation increases stress-induced alcohol consumption in primates. Proceedings of the National Academy of Sciences of the United States of America 106:14593-14598.
Barr CS, Dvoskin RL, Yuan Q, Lipsky RH, Gupte M, Hu X, Zhou Z, Schwandt ML, Lindell SG, McKee M, Becker ML, Kling MA, Gold PW, Higley D, Heilig M, Suomi SJ, Goldman D (2008) CRH haplotype as a factor influencing cerebrospinal fluid levels of corticotropin-releasing hormone, hypothalamic-pituitary-adrenal axis activity, temperament, and alcohol consumption in rhesus macaques. Archives of general psychiatry 65:934-944.
Bartlett S, Heilig M (2013) Translational approaches to medication development. Current topics in behavioral neurosciences 13:543-582.
Bjork K, Terasmaa A, Sun H, Thorsell A, Sommer WH, Heilig M (2010) Ethanol-induced activation of AKT and DARPP-32 in the mouse striatum mediated by opioid receptors. Addiction biology 15:299-303.
Bjork K, Rimondini R, Hansson AC, Terasmaa A, Hyytia P, Heilig M, Sommer WH (2008) Modulation of voluntary ethanol consumption by beta-arrestin 2. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 22:2552-2560.
Breese GR, Sinha R, Heilig M (2011) Chronic alcohol neuroadaptation and stress contribute to susceptibility for alcohol craving and relapse. Pharmacology & therapeutics 129:149-171.
Cannella N, Economidou D, Kallupi M, Stopponi S, Heilig M, Massi M, Ciccocioppo R (2009) Persistent increase of alcohol-seeking evoked by neuropeptide S: an effect mediated by the hypothalamic hypocretin system. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 34:2125-2134.
Cippitelli A, Karlsson C, Shaw JL, Thorsell A, Gehlert DR, Heilig M (2010) Suppression of alcohol self-administration and reinstatement of alcohol seeking by melanin-concentrating hormone receptor 1 (MCH1-R) antagonism in Wistar rats. Psychopharmacology 211:367-375.
Cippitelli A, Zook M, Bell L, Damadzic R, Eskay RL, Schwandt M, Heilig M (2010) Reversibility of object recognition but not spatial memory impairment following binge-like alcohol exposure in rats. Neurobiology of learning and memory 94:538-546.
Cippitelli A, Damadzic R, Hamelink C, Brunnquell M, Thorsell A, Heilig M, Eskay RL (2012) Binge-like ethanol consumption increases corticosterone levels and neurodegneration whereas occupancy of type II glucocorticoid receptors with mifepristone is neuroprotective. Addiction biology.
Cippitelli A, Damadzic R, Singley E, Thorsell A, Ciccocioppo R, Eskay RL, Heilig M (2012) Pharmacological blockade of corticotropin-releasing hormone receptor 1 (CRH1R) reduces voluntary consumption of high alcohol concentrations in non-dependent Wistar rats. Pharmacology, biochemistry, and behavior 100:522-529.
Cippitelli A, Damadzic R, Frankola K, Goldstein A, Thorsell A, Singley E, Eskay RL, Heilig M (2010) Alcohol-induced neurodegeneration, suppression of transforming growth factor-beta, and cognitive impairment in rats: prevention by group II metabotropic glutamate receptor activation. Biological psychiatry 67:823-830.
Cippitelli A, Damadzic R, Hansson AC, Singley E, Sommer WH, Eskay R, Thorsell A, Heilig M (2010) Neuropeptide Y (NPY) suppresses yohimbine-induced reinstatement of alcohol seeking. Psychopharmacology 208:417-426.
Cippitelli A, Rezvani AH, Robinson JE, Eisenberg L, Levin ED, Bonaventure P, Motley ST, Lovenberg TW, Heilig M, Thorsell A (2011) The novel, selective, brain-penetrant neuropeptide Y Y2 receptor antagonist, JNJ-31020028, tested in animal models of alcohol consumption, relapse, and anxiety. Alcohol 45:567-576.
Economidou D, Hansson AC, Weiss F, Terasmaa A, Sommer WH, Cippitelli A, Fedeli A, Martin-Fardon R, Massi M, Ciccocioppo R, Heilig M (2008) Dysregulation of nociceptin/orphanin FQ activity in the amygdala is linked to excessive alcohol drinking in the rat. Biological psychiatry 64:211-218.
George DT, Gilman J, Hersh J, Thorsell A, Herion D, Geyer C, Peng X, Kielbasa W, Rawlings R, Brandt JE, Gehlert DR, Tauscher JT, Hunt SP, Hommer D, Heilig M (2008) Neurokinin 1 receptor antagonism as a possible therapy for alcoholism. Science 319:1536-1539.
Hansson AC, Rimondini R, Neznanova O, Sommer WH, Heilig M (2008) Neuroplasticity in brain reward circuitry following a history of ethanol dependence. The European journal of neuroscience 27:1912-1922.
Hansson AC, Nixon K, Rimondini R, Damadzic R, Sommer WH, Eskay R, Crews FT, Heilig M (2010) Long-term suppression of forebrain neurogenesis and loss of neuronal progenitor cells following prolonged alcohol dependence in rats. The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum 13:583-593.
Heilig M, Egli M, Crabbe JC, Becker HC (2010) Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked? Addiction biology 15:169-184.
Heilig M, Goldman D, Berrettini W, O'Brien CP (2011) Pharmacogenetic approaches to the treatment of alcohol addiction. Nature reviews Neuroscience 12:670-684.
Heilig M, Thorsell A, Sommer WH, Hansson AC, Ramchandani VA, George DT, Hommer D, Barr CS (2010) Translating the neuroscience of alcoholism into clinical treatments: from blocking the buzz to curing the blues. Neuroscience and biobehavioral reviews 35:334-344.
Jerlhag E, Egecioglu E, Landgren S, Salome N, Heilig M, Moechars D, Datta R, Perrissoud D, Dickson SL, Engel JA (2009) Requirement of central ghrelin signaling for alcohol reward. Proceedings of the National Academy of Sciences of the United States of America 106:11318-11323.
Kallupi M, Cannella N, Economidou D, Ubaldi M, Ruggeri B, Weiss F, Massi M, Marugan J, Heilig M, Bonnavion P, de Lecea L, Ciccocioppo R (2010) Neuropeptide S facilitates cue-induced relapse to cocaine seeking through activation of the hypothalamic hypocretin system. Proceedings of the National Academy of Sciences of the United States of America 107:19567-19572.
Karlsson RM, Tanaka K, Heilig M, Holmes A (2008) Loss of glial glutamate and aspartate transporter (excitatory amino acid transporter 1) causes locomotor hyperactivity and exaggerated responses to psychotomimetics: rescue by haloperidol and metabotropic glutamate 2/3 agonist. Biological psychiatry 64:810-814.
Karlsson RM, Tanaka K, Saksida LM, Bussey TJ, Heilig M, Holmes A (2009) Assessment of glutamate transporter GLAST (EAAT1)-deficient mice for phenotypes relevant to the negative and executive/cognitive symptoms of schizophrenia. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 34:1578-1589.
Karlsson RM, Choe JS, Cameron HA, Thorsell A, Crawley JN, Holmes A, Heilig M (2008) The neuropeptide Y Y1 receptor subtype is necessary for the anxiolytic-like effects of neuropeptide Y, but not the antidepressant-like effects of fluoxetine, in mice. Psychopharmacology 195:547-557.
Karlsson C, Zook M, Ciccocioppo R, Gehlert DR, Thorsell A, Heilig M, Cippitelli A (2012) Melanin-concentrating hormone receptor 1 (MCH1-R) antagonism: reduced appetite for calories and suppression of addictive-like behaviors. Pharmacology, biochemistry, and behavior 102:400-406.
Karlsson RM, Adermark L, Molander A, Perreau-Lenz S, Singley E, Solomon M, Holmes A, Tanaka K, Lovinger DM, Spanagel R, Heilig M (2012) Reduced alcohol intake and reward associated with impaired endocannabinoid signaling in mice with a deletion of the glutamate transporter GLAST. Neuropharmacology 63:181-189.
Leeman RF, Heilig M, Cunningham CL, Stephens DN, Duka T, O'Malley SS (2010) Ethanol consumption: how should we measure it? Achieving consilience between human and animal phenotypes. Addiction biology 15:109-124.
Lindell SG, Schwandt ML, Sun H, Sparenborg JD, Bjork K, Kasckow JW, Sommer WH, Goldman D, Higley JD, Suomi SJ, Heilig M, Barr CS (2010) Functional NPY variation as a factor in stress resilience and alcohol consumption in rhesus macaques. Archives of general psychiatry 67:423-431.
Litten RZ, Egli M, Heilig M, Cui C, Fertig JB, Ryan ML, Falk DE, Moss H, Huebner R, Noronha A (2012) Medications development to treat alcohol dependence: a vision for the next decade. Addiction biology 17:513-527.
Liu K, Southall N, Titus SA, Inglese J, Eskay RL, Shinn P, Austin CP, Heilig MA, Zheng W (2010) A multiplex calcium assay for identification of GPCR agonists and antagonists. Assay and drug development technologies 8:367-379.
Mahmoud S, Thorsell A, Sommer WH, Heilig M, Holgate JK, Bartlett SE, Ruiz-Velasco V (2011) Pharmacological consequence of the A118G mu opioid receptor polymorphism on morphine- and fentanyl-mediated modulation of Ca(2)(+) channels in humanized mouse sensory neurons. Anesthesiology 115:1054-1062.
Marugan J, Liu K, Zheng W, Eskay R, Southall N, Heilig M, Inglese J, Austin C (2010) Identification of Functionally Selective Small Molecule Antagonists of the Neuropeptide-S Receptor: Naphthopyranopyrimidines. In: Probe Reports from the NIH Molecular Libraries Program. Bethesda (MD).
McCoy JG, Marugan JJ, Liu K, Zheng W, Southall N, Huang W, Heilig M, Austin CP (2010) Selective Modulation of Gq/Gs pathways by Naphtho Pyrano Pyrimidines as antagonists of the Neuropeptide S Receptor. ACS chemical neuroscience 1:559-574.
Molander A, Vengeliene V, Heilig M, Wurst W, Deussing JM, Spanagel R (2012) Brain-specific inactivation of the Crhr1 gene inhibits post-dependent and stress-induced alcohol intake, but does not affect relapse-like drinking. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 37:1047-1056.
Neznanova O, Bjork K, Rimondini R, Hansson AC, Hyytia P, Heilig M, Sommer WH (2009) Acute ethanol challenge inhibits glycogen synthase kinase-3beta in the rat prefrontal cortex. The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum 12:275-280.
Patnaik S, Marugan J, Liu K, Zheng W, Thorsell A, Eskay R, Southall N, Heilig M, Inglese J, Austin C (2010) Identification of Small Molecule Antagonists of the Neuropeptide-S Receptor. In: Probe Reports from the NIH Molecular Libraries Program. Bethesda (MD).
Pickens CL, Adams-Deutsch T, Nair SG, Navarre BM, Heilig M, Shaham Y (2009) Effect of pharmacological manipulations of neuropeptide Y and corticotropin-releasing factor neurotransmission on incubation of conditioned fear. Neuroscience 164:1398-1406.
Rimondini R, Sommer WH, Dall'Olio R, Heilig M (2008) Long-lasting tolerance to alcohol following a history of dependence. Addiction biology 13:26-30.
Robinson JE, Fish EW, Krouse MC, Thorsell A, Heilig M, Malanga CJ (2012) Potentiation of brain stimulation reward by morphine: effects of neurokinin-1 receptor antagonism. Psychopharmacology 220:215-224.
Schank JR, Ryabinin AE, Giardino WJ, Ciccocioppo R, Heilig M (2012) Stress-related neuropeptides and addictive behaviors: beyond the usual suspects. Neuron 76:192-208.
Schank JR, Pickens CL, Rowe KE, Cheng K, Thorsell A, Rice KC, Shaham Y, Heilig M (2011) Stress-induced reinstatement of alcohol-seeking in rats is selectively suppressed by the neurokinin 1 (NK1) antagonist L822429. Psychopharmacology 218:111-119.
Schank JR, Goldstein AL, Rowe KE, King CE, Marusich JA, Wiley JL, Carroll FI, Thorsell A, Heilig M (2012) The kappa opioid receptor antagonist JDTic attenuates alcohol seeking and withdrawal anxiety. Addiction biology 17:634-647.
Schwandt ML, Higley JD, Suomi SJ, Heilig M, Barr CS (2008) Rapid tolerance and locomotor sensitization in ethanol-naive adolescent rhesus macaques. Alcoholism, clinical and experimental research 32:1217-1228.
Schwandt ML, Lindell SG, Higley JD, Suomi SJ, Heilig M, Barr CS (2011) OPRM1 gene variation influences hypothalamic-pituitary-adrenal axis function in response to a variety of stressors in rhesus macaques. Psychoneuroendocrinology 36:1303-1311.
Schwandt ML, Lindell SG, Chen S, Higley JD, Suomi SJ, Heilig M, Barr CS (2010) Alcohol response and consumption in adolescent rhesus macaques: life history and genetic influences. Alcohol 44:67-80.
Schwandt ML, Lindell SG, Sjoberg RL, Chisholm KL, Higley JD, Suomi SJ, Heilig M, Barr CS (2010) Gene-environment interactions and response to social intrusion in male and female rhesus macaques. Biological psychiatry 67:323-330.
Sinha R, Shaham Y, Heilig M (2011) Translational and reverse translational research on the role of stress in drug craving and relapse. Psychopharmacology 218:69-82.
Skinbjerg M, Ariano MA, Thorsell A, Heilig M, Halldin C, Innis RB, Sibley DR (2009) Arrestin3 mediates D(2) dopamine receptor internalization. Synapse 63:621-624.
Skinbjerg M, Liow JS, Seneca N, Hong J, Lu S, Thorsell A, Heilig M, Pike VW, Halldin C, Sibley DR, Innis RB (2010) D2 dopamine receptor internalization prolongs the decrease of radioligand binding after amphetamine: a PET study in a receptor internalization-deficient mouse model. NeuroImage 50:1402-1407.
Sommer WH, Rimondini R, Hansson AC, Hipskind PA, Gehlert DR, Barr CS, Heilig MA (2008) Upregulation of voluntary alcohol intake, behavioral sensitivity to stress, and amygdala crhr1 expression following a history of dependence. Biological psychiatry 63:139-145.
Sommer WH, Lidstrom J, Sun H, Passer D, Eskay R, Parker SC, Witt SH, Zimmermann US, Nieratschker V, Rietschel M, Margulies EH, Palkovits M, Laucht M, Heilig M (2010) Human NPY promoter variation rs16147:T>C as a moderator of prefrontal NPY gene expression and negative affect. Human mutation 31:E1594-1608.
Stephens DN, Duka T, Crombag HS, Cunningham CL, Heilig M, Crabbe JC (2010) Reward sensitivity: issues of measurement, and achieving consilience between human and animal phenotypes. Addiction biology 15:145-168.
Stopponi S, Somaini L, Cippitelli A, Cannella N, Braconi S, Kallupi M, Ruggeri B, Heilig M, Demopulos G, Gaitanaris G, Massi M, Ciccocioppo R (2011) Activation of nuclear PPARgamma receptors by the antidiabetic agent pioglitazone suppresses alcohol drinking and relapse to alcohol seeking. Biological psychiatry 69:642-649.
Tapocik JD, Solomon M, Flanigan M, Meinhardt M, Barbier E, Schank JR, Schwandt M, Sommer WH, Heilig M (2012) Coordinated dysregulation of mRNAs and microRNAs in the rat medial prefrontal cortex following a history of alcohol dependence. The pharmacogenomics journal.
Thorsell A, Schank JR, Singley E, Hunt SP, Heilig M (2010) Neurokinin-1 receptors (NK1R:s), alcohol consumption, and alcohol reward in mice. Psychopharmacology 209:103-111.
Vendruscolo LF, Barbier E, Schlosburg JE, Misra KK, Whitfield TW, Jr., Logrip ML, Rivier C, Repunte-Canonigo V, Zorrilla EP, Sanna PP, Heilig M, Koob GF (2012) Corticosteroid-dependent plasticity mediates compulsive alcohol drinking in rats. The Journal of neuroscience : the official journal of the Society for Neuroscience 32:7563-7571.
Zorrilla EP, Heilig M, de Wit H, Shaham Y (2013) Behavioral, biological, and chemical perspectives on targeting CRF(1) receptor antagonists to treat alcoholism. Drug and alcohol dependence.
REVIEWS AND BOOK CHAPTERS
Heilig M, Koob GF. A key role for corticotropin-releasing factor in alcohol dependence. Trends Neurosci 2007;30(8):399-406. PubMed
Heilig M, Egli M. Pharmacological treatment of alcohol dependence: Target symptoms and target mechanisms. Pharm Therap 2006;111(3):855-76. PubMed
Thorsell A, Karlsson RM, Heilig M. NPY in alcoholism and psychiatric disorders. EXS 2006;(95):183-92. PubMed
Heilig M, Thiele TE. Neuropeptide Y antagonists: a perspective. In: Spanagel R, Mann K, editors. Drugs for Relapse Prevention of Alcoholism.Basel: Birkhaüser; 2005. p. 189-205.
Heilig M, Egli M. Models for alcohol dependence: A clinical perspective. Drug Discov Today: Dis Models 2005;2(4):313-8.
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