Photo of Markus Heilig

Markus Heilig, MD, PhD, Chief
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
telephone: 301.435.9386
e-mail: markus.heilig@mail.nih.gov

 

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.

 

Current staff

Jenica Tapocik, PhD
Staff Scientist
telephone: 301.402.5305
tapocikjd@mail.nih.gov

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
Chemist
telephone: 301.496.4936
erick.singley@mail.nih.gov

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
Biologist
telephone: 301.451.5059
hui.sun@mail.nih.gov

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
Research Physiologist
telephone: 301.496.4690
bob.eskay@mail.nih.gov

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
Biologist
telephone: 301.451.9472
ruslan.damadzic@mail.nih.gov

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
Post-Doctoral IRTA
telephone: 301.451.7605
estelle.barbier@nih.gov

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
Post-Doctoral IRTA
telephone: 301.594.0633
jesse.schank@nih.gov

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
Post-Doctoral IRTA

 

Camilla Karlsson
Pre-Doctoral IRTA
telephone: 301.435.9276
camilla.karlsson@nih.gov

 

Courtney King
Post-Bacc IRTA
telephone: 301.451.8855
courtney.king@nih.gov

 

Meghan Flanigan
Post-Bacc IRTA
telephone: 301.496.8106
meghan.flanigan@nih.gov

Meghan Flanigan joined MP in June 2011 after receiving her B.A. degree in Neuroscience from Pomona College in California. Meghan is working with Dr. Tapocik on investigating how mRNAs and microRNAs (miRNAs) are involved in alcohol dependence using a "post dependent" rat model in line with mRNA and miRNA expression profiling.

 

Nathan Juergens
Post-Bacc IRTA
telephone: 301.451.6969
nathan.juergens@nih.gov

Nathan Juergens joined MP in June 2011 after receiving his B.A. degree in Biology from Macalester College in St. Paul, Minnesota. Nathan is studying the effects of alcohol abuse on epigenetic patterning in the rat genome and observing differential rat behavior via modulation of these epigenetic pathways.

  Faaz Rehman, BS
Post-Bacc IRTA
  Matthew Solomon, BS
Technical IRTA
  Alexandra Pincus, BS
Technical IRTA

 

Selected Publications

ORIGINAL PAPERS

Schwandt ML, Lindell SG, Higley JD, Suomi SJ, Heilig M, Barr CS. OPRM1 gene variation influences hypothalamic-pituitary-adrenal axis function in response to a variety of stressors in rhesus macaques. Psychoneuroendocrinology. 2011 Apr 2. [Epub ahead of print] PubMed

Patnaik S, Marugan J, Liu K, Zheng W, Thorsell A, Eskay R, Southall N, Heilig M, Inglese J, Austin C. Identification of Small Molecule Antagonists of the Neuropeptide-S Receptor. 2010 Mar 19 [updated 2010 Dec 16]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available from Bookshelf

Marugan J, Liu K, Zheng W, Eskay R, Southall N, Heilig M, Inglese J, Austin C. Identification of Functionally Selective Small Molecule Antagonists of the Neuropeptide-S Receptor: Naphthopyranopyrimidines. 2009 Feb 13 [updated 2010 Sep 2]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available from Bookshelf

Sinha R, Shaham Y, Heilig M. Translational and reverse translational research on the role of stress in drug craving and relapse. Psychopharmacology (Berl). 2011 Apr 15. [Epub ahead of print] PubMed

Schank JR, Pickens CL, Rowe KE, Cheng K, Thorsell A, Rice KC, Shaham Y, Heilig M. Stress-induced reinstatement of alcohol-seeking in rats is selectively suppressed by the neurokinin 1 (NK1) antagonist L822429. Psychopharmacology (Berl). 2011 Feb 22. [Epub ahead of print] PubMed

Copeland WE, Magnusson A, Göransson M, Heilig MA. Genetic moderators and psychiatric mediators of the link between sexual abuse and alcohol dependence. Drug Alcohol Depend. 2010 Dec 28. [Epub ahead of print] PubMed

Hansson AC, Rimondini R, Heilig M, Mathé AA, Sommer WH. Dissociation of antidepressant-like activity of escitalopram and nortriptyline on behaviour and hippocampal BDNF expression in female rats. J Psychopharmacol. 2011 Jan 24. [Epub ahead of print] PubMed

Heilig M, Warren KR, Kunos G, Silverman PB, Hewitt BG. Addiction Research Centres and the Nurturing of Creativity. Addiction. 2010 Jun 21. [Epub ahead of print] PubMed

Ramchandani VA, Umhau J, Pavon FJ, Ruiz-Velasco V, Margas W, Sun H, Damadzic R, Eskay R, Schoor M, Thorsell A, Schwandt ML, Sommer WH, George DT, Parsons LH, Herscovitch P, Hommer D, Heilig M. A genetic determinant of the striatal dopamine response to alcohol in men. Mol Psychiatry. 2010 May 18. [Epub ahead of print] PubMed

Copeland WE, Sun H, Costello EJ, Angold A, Heilig MA, Barr CS. Child µ-Opioid Receptor Gene Variant Influences Parent-Child Relations. Neuropsychopharmacology. 2011 May;36(6):1165-70. PubMed

Heilig M. A welcome change that stops short of being fully satisfying. Addiction. 2011 May;106(5):874-5. PubMed

Stopponi S, Somaini L, Cippitelli A, Cannella N, Braconi S, Kallupi M, Ruggeri B, Heilig M, Demopulos G, Gaitanaris G, Massi M, Ciccocioppo R. Activation of nuclear PPAR? receptors by the antidiabetic agent pioglitazone suppresses alcohol drinking and relapse to alcohol seeking. Biol Psychiatry. 2011 Apr 1;69(7):642-9. PubMed

Rinker JA, Hutchison MA, Chen SA, Thorsell A, Heilig M, Riley AL. Exposure to nicotine during periadolescence or early adulthood alters aversive and physiological effects induced by ethanol. Pharmacol Biochem Behav. 2011 Mar 21;99(1):7-16. PubMed

Breese GR, Sinha R, Heilig M. Chronic alcohol neuroadaptation and stress contribute to susceptibility for alcohol craving and relapse. Pharmacol Ther.2011 Feb;129(2):149-71. PubMed

Blom ES, Wang Y, Skoglund L, Hansson AC, Ubaldi M, Lourdusamy A, Sommer WH, Mielke M, Hyman BT, Heilig M, Lannfelt L, Nilsson LN, Ingelsson M. Increased mRNA Levels of TCF7L2 and MYC of the Wnt Pathway in Tg-ArcSwe Mice and Alzheimer's Disease Brain. Int J Alzheimers Dis. 2010 Dec 22;2011:936580. PubMed

Cippitelli A, Rezvani AH, Robinson JE, Eisenberg L, Levin ED, Bonaventure P, Motley ST, Lovenberg TW, Heilig M, Thorsell A. The novel, selective, brain-penetrant neuropeptide Y Y2 receptor antagonist, JNJ-31020028, tested in animal models of alcohol consumption, relapse, and anxiety. Alcohol. 2010 Dec 10. [Epub ahead of print] PubMed

Cippitelli A, Zook M, Bell L, Damadzic R, Eskay RL, Schwandt M, Heilig M. Reversibility of object recognition but not spatial memory impairment following binge-like alcohol exposure in rats. Neurobiol Learn Mem. 2010 Nov;94(4):538-46. PubMed

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. Neuropeptide S facilitates cue-induced relapse to cocaine seeking through activation of the hypothalamic hypocretin system. Proc Natl Acad Sci U S A. 2010 Nov 9;107(45):19567-72. PubMed

Heilig M, Thorsell A, Sommer WH, Hansson AC, Ramchandani VA, George DT, Hommer D, Barr CS. Translating the neuroscience of alcoholism into clinical treatments: From blocking the buzz to curing the blues. Neurosci Biobehav Rev. 2010 Nov;35(2):334-44. PubMed

Umhau JC, Momenan R, Schwandt ML, Singley E, Lifshitz M, Doty L, Adams LJ, Vengeliene V, Spanagel R, Zhang Y, Shen J, George DT, Hommer D, Heilig M. Effect of acamprosate on magnetic resonance spectroscopy measures of central glutamate in detoxified alcohol-dependent individuals: a randomized controlled experimental medicine study. Arch Gen Psychiatry. 2010 Oct;67(10):1069-77. PubMed

Cippitelli A, Karlsson C, Shaw JL, Thorsell A, Gehlert DR, Heilig M. Suppression of alcohol self-administration and reinstatement of alcohol seeking by melanin-concentrating hormone receptor 1 (MCH1-R) antagonism in Wistar rats. Psychopharmacology (Berl). 2010 Sep;211(4):367-75. PubMed

McCoy JG, Marugan JJ, Liu K, Zheng W, Southall N, Huang W, Heilig M, Austin CP. Selective Modulation of Gq/Gs pathways by Naphtho Pyrano Pyrimidines as antagonists of the Neuropeptide S Receptor. ACS Chem Neurosci. 2010 Aug 18;1(8):559-574. PubMed

Sommer WH, Lidström 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. Human NPY promoter variation rs16147:T>C as a moderator of prefrontal NPY gene expression and negative affect. Hum Mutat. 2010 Aug;31(8):E1594-608. PubMed

Björk K, Terasmaa A, Sun H, Thorsell A, Sommer WH, Heilig M. Ethanol-induced activation of AKT and DARPP-32 in the mouse striatum mediated by opioid receptors. Addict Biol. 2010 Jul;15(3):299-303. PubMed

Hansson AC, Nixon K, Rimondini R, Damadzic R, Sommer WH, Eskay R, Crews FT, Heilig M. Long-term suppression of forebrain neurogenesis and loss of neuronal progenitor cells following prolonged alcohol dependence in rats. Int J Neuropsychopharmacol. 2010 Jun;13(5):583-93. PubMed

Liu K, Southall N, Titus SA, Inglese J, Eskay RL, Shinn P, Austin CP, Heilig MA, Zheng W. A multiplex calcium assay for identification of GPCR agonists and antagonists. Assay Drug Dev Technol. 2010 Jun;8(3):367-79. PubMed

Spinelli S, Chefer S, Carson RE, Jagoda E, Lang L, Heilig M, Barr CS, Suomi SJ, Higley JD, Stein EA. Effects of early-life stress on serotonin(1A) receptors in juvenile Rhesus monkeys measured by positron emission tomography. Biol Psychiatry. 2010 Jun 15;67(12):1146-53. PubMed

Cippitelli A, Damadzic R, Frankola K, Goldstein A, Thorsell A, Singley E, Eskay RL, Heilig M. Alcohol-Induced Neurodegeneration, Suppression of Transforming Growth Factor-beta, and Cognitive Impairment in Rats: Prevention by Group II Metabotropic Glutamate Receptor Activation. Biol Psychiatry. 2010 May 1;67(9):823-30. PubMed

Umhau JC, Schwandt ML, Usala J, Geyer C, Singley E, George DT, Heilig M. Pharmacologically induced alcohol craving in treatment seeking alcoholics correlates with alcoholism severity, but is insensitive to acamprosate. Neuropsychopharmacology. 2011 May;36(6):1178-86. PubMed

Skinbjerg M, Liow JS, Seneca N, Hong J, Lu S, Thorsell A, Heilig M, Pike VW, Halldin C, Sibley DR, Innis RB. D(2) dopamine receptor internalization prolongs the decrease of radioligand binding after amphetamine: A PET study in a receptor internalization-deficient mouse model. Neuroimage. 2010 May 1;50(4):1402-7. PubMed

Heilig M, Egli M, Crabbe JC, Becker HC. Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked? Addict Biol. 2010 Apr;15(2):169-84. PubMed

Lindell SG, Schwandt ML, Sun H, Sparenborg JD, Björk K, Kasckow JW, Sommer WH, Goldman D, Higley JD, Suomi SJ, Heilig M, Barr CS. Functional NPY variation as a factor in stress resilience and alcohol consumption in rhesus macaques. Arch Gen Psychiatry. 2010 Apr;67(4):423-31. PubMed

Stephens DN, Duka T, Crombag HS, Cunningham CL, Heilig M, Crabbe JC. Reward sensitivity: issues of measurement, and achieving consilience between human and animal phenotypes. Addict Biol. 2010 Apr;15(2):145-68. PubMed

Leeman RF, Heilig M, Cunningham CL, Stephens DN, Duka T, O'Malley SS. Ethanol consumption: how should we measure it? Achieving consilience between human and animal phenotypes. Addict Biol. 2010 Apr;15(2):109-24. PubMed

Magnusson A, Göransson M, Heilig M. Early onset alcohol dependence with high density of family history is not "male limited". Alcohol. 2010 Mar;44(2):131-9. PubMed

Thorsell A, Schank JR, Singley E, Hunt SP, Heilig M. Neurokinin-1 receptors (NK1R:s), alcohol consumption, and alcohol reward in mice. Psychopharmacology (Berl). 2010 Mar;209(1):103-11. PubMed

Schwandt ML, Lindell SG, Sjöberg RL, Chisholm KL, Higley JD, Suomi SJ, Heilig M, Barr CS. Gene-environment interactions and response to social intrusion in male and female rhesus macaques. Biol Psychiatry. 2010 Feb 15;67(4):323-30. PubMed

Schwandt ML, Lindell SG, Chen S, Higley JD, Suomi SJ, Heilig M, Barr CS. Alcohol response and consumption in adolescent rhesus macaques: life history and genetic influences. Alcohol. 2010 Feb;44(1):67-80. PubMed

Cippitelli A, Damadzic R, Hansson AC, Singley E, Sommer WH, Eskay R, Thorsell A, Heilig M. Neuropeptide Y (NPY) suppresses yohimbine-induced reinstatement of alcohol seeking. Psychopharmacology (Berl). 2010 Feb;208(3):417-26. PubMed

Barr CS, Chen SA, Schwandt ML, Lindell SG, Sun H, Suomi SJ, Heilig M. Suppression of alcohol preference by naltrexone in the rhesus macaque: a critical role of genetic variation at the micro-opioid receptor gene locus. Biol Psychiatry. 2010 Jan 1;67(1):78-80. PubMed

George DT, Herion DW, Jones CL, Phillips MJ, Hersh J, Hill D, Heilig M, Ramchandani VA, Geyer C, Spero DE, Singley ED, O'Malley SS, Bishai R, Rawlings RR, Kunos G. Rimonabant (SR141716) has no effect on alcohol self-administration or endocrine measures in nontreatment-seeking heavy alcohol drinkers. Psychopharmacology (Berl). 2010 Jan; 208(1):37-44. PubMed

Pickens CL, Adams-Deutsch T, Nair SG, Navarre BM, Heilig M, Shaham Y. Effect of pharmacological manipulations of neuropeptide Y and corticotropin-releasing factor neurotransmission on incubation of conditioned fear. Neuroscience. 2009 Dec 29;164(4):1398-406. PubMed PubMed

Barr CS, Dvoskin RL, Gupte M, Sommer W, Sun H, Schwandt ML, Lindell SG, Kasckow JW, Suomi SJ, Goldman D, Higley JD, Heilig M. Functional CRH variation increases stress-induced alcohol consumption in primates. Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14593-8. PubMed

Cannella N, Economidou D, Kallupi M, Stopponi S, Heilig M, Massi M, Ciccocioppo R. Persistent increase of alcohol-seeking evoked by neuropeptide S: an effect mediated by the hypothalamic hypocretin system. Neuropsychopharmacology. 2009 Aug;34(9):2125-34. PubMed

Jerlhag E, Egecioglu E, Landgren S, Salomé N, Heilig M, Moechars D, Datta R, Perrissoud D, Dickson SL, Engel JA. Requirement of central ghrelin signaling for alcohol reward. Proc Natl Acad Sci U S A. 2009 Jul 7;106(27):11318-23. PubMed

Skinbjerg M, Ariano MA, Thorsell A, Heilig M, Halldin C, Innis RB, Sibley DR. Arrestin3 mediates D(2) dopamine receptor internalization. Synapse. 2009 Jul;63(7):621-4. PubMed

Karlsson RM, Tanaka K, Heilig M, Holmes A. 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. Biol Psychiatry. 2008 Nov 1;64(9):810-4. PubMed

Kakko J, von Wachenfeldt J, Svanborg KD, Lidström J, Barr CS, Heilig M. Mood and neuroendocrine response to a chemical stressor, metyrapone, in buprenorphine-maintained heroin dependence. Biol Psychiatry. 2008 Jan 15;63(2):172-7. Erratum in: Biol Psychiatry. 2008 Sep 15;64(6):545. PubMed

Economidou D, Hansson AC, Weiss F, Terasmaa A, Sommer WH, Cippitelli A, Fedeli A, Martin-Fardon R, Massi M, Ciccocioppo R, Heilig M. Dysregulation of nociceptin/orphanin FQ activity in the amygdala is linked to excessive alcohol drinking in the rat. Biol Psychiatry. 2008 Aug 1;64(3):211-8. PubMed

Björk K, Rimondini R, Hansson AC, Terasmaa A, Hyytiä P, Heilig M, Sommer WH. Modulation of voluntary ethanol consumption by beta-arrestin 2. FASEB J. 2008 Jul;22(7):2552-60.PubMed

Hansson AC, Rimondini R, Neznanova O, Sommer WH, Heilig M. Neuroplasticity in brain reward circuitry following a history of ethanol dependence. Eur J Neurosci. 2008 Apr;27(8):1912-22. PubMed

Barr CS, Schwandt ML, Lindell SG, Higley JD, Maestripieri D, Goldman D, Suomi SJ, Heilig M. Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates. Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5277-81. PubMed

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. Neurokinin 1 receptor antagonism as a possible therapy for alcoholism. Science. 2008 Mar 14;319(5869):1536-9. PubMed

Sommer WH, Rimondini R, Hansson AC, Hipskind PA, Gehlert DR, Barr CS, Heilig MA. Upregulation of voluntary alcohol intake, behavioral sensitivity to stress, and amygdala crhr1 expression following a history of dependence. Biol Psychiatry. 2008 Jan 15;63(2):139-45.PubMed

Karlsson RM, Choe JS, Cameron HA, Thorsell A, Crawley JN, Holmes A, Heilig M. 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 (Berl). 2008 Jan;195(4):547-57. PubMed

Hansson AC, Cippitelli A, Sommer WH, Fedeli A, Björk K, Soverchia L, Terasmaa A, Massi M, Heilig M, Ciccocioppo R. Variation at the rat Crhr1 locus and sensitivity to relapse into alcohol seeking induced by environmental stress. Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15236-41. PubMed

Sommer WH, Rimondini R, Marquitz M, Lidström J, Siems WE, Bader M, Heilig M. Plasticity and impact of the central renin-angiotensin system during development of ethanol dependence. J Mol Med. 2007 Oct;85(10):1089-97. PubMed

Thorsell A, Johnson J, Heilig M. Effect of the adenosine A2a receptor antagonist 3,7-dimethyl-propargylxanthine on anxiety-like and depression-like behavior and alcohol consumption in Wistar Rats. Alcohol Clin Exp Res. 2007 Aug;31(8):1302-7. PubMed

Kakko J, Grönbladh L, Svanborg KD, von Wachenfeldt J, Rück C, Rawlings B, Nilsson LH, Heilig M. A stepped care strategy using buprenorphine and methadone versus conventional methadone maintenance in heroin dependence: a randomized controlled trial. Am J Psychiatry. 2007 May;164(5):797-803. PubMed

Barr CS, Schwandt M, Lindell SG, Chen SA, Goldman D, Suomi SJ, Higley JD, Heilig M. Association of a functional polymorphism in the mu-opioid receptor gene with alcohol response and consumption in male rhesus macaques. Arch Gen Psychiatry. 2007 Mar;64(3):369-76. PubMed

Gehlert DR, Cippitelli A, Thorsell A, Lê AD, Hipskind PA, Hamdouchi C, Lu J, Hembre EJ, Cramer J, Song M, McKinzie D, Morin M, Ciccocioppo R, Heilig M. 3-(4-Chloro-2-morpholin-4-yl-thiazol-5-yl)-8-(1-ethylpropyl)-2,6-dimethyl-imidazo [1,2-b]pyridazine: a novel brain-penetrant, orally available corticotropin-releasing factor receptor 1 antagonist with efficacy in animal models of alcoholism. J Neurosci. 2007 Mar 7;27(10):2718-26. PubMed

Ciccocioppo R, Economidou D, Rimondini R, Sommer W, Massi M, Heilig M. Buprenorphine reduces alcohol drinking through activation of the nociceptin/orphanin FQ-NOP receptor system. Biol Psychiatry. 2007 Jan 1;61(1):4-12. PubMed

Hansson AC, Bermúdez-Silva FJ, Malinen H, Hyytiä P, Sanchez-Vera I, Rimondini R, Rodriguez de Fonseca F, Kunos G, Sommer WH, Heilig M. Genetic impairment of frontocortical endocannabinoid degradation and high alcohol preference. Neuropsychopharmacology. 2007 Jan;32(1):117-26. PubMed

Rydmark I, Wahlberg K, Ghatan PH, Modell S, Nygren A, Ingvar M, Asberg M, Heilig M. Neuroendocrine, cognitive and structural imaging characteristics of women on longterm sickleave with job stress-induced depression. Biol Psychiatry. 2006 Oct 15;60(8):867-73. PubMed

Bart G, Kreek MJ, Ott J, LaForge KS, Proudnikov D, Pollak L, Heilig M. Increased attributable risk related to a functional mu-opioid receptor gene polymorphism in association with alcohol dependence in central Sweden. Neuropsychopharmacology. 2005 Feb;30(2):417-22. PubMed

REVIEWS AND BOOK CHAPTERS

Ciccocioppo R, Gehlert DR, Ryabinin A, Kaur S, Cippitelli A, Thorsell A, Lê AD, Hipskind PA, Hamdouchi C, Lu J, Hembre EJ, Cramer J, Song M, McKinzie D, Morin M, Economidou D, Stopponi S, Cannella N, Braconi S, Kallupi M, de Guglielmo G, Massi M, George DT, Gilman J, Hersh J, Tauscher JT, Hunt SP, Hommer D, Heilig M. Stress-related neuropeptides and alcoholism: CRH, NPY, and beyond. Alcohol. 2009 Nov;43(7):491-8. PubMed

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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