Heads of Laboratories
Patrick E. and Beatrice M. Haggerty Professor
Senior Attending Physician
Laboratory of the Biology of Addictive Diseases
An estimated 25 to 33 percent of people who take a short-acting opiate drug — usually heroin — develop an addiction to it. This suggests some people are naturally more vulnerable to addiction than others and that genetics may play a role. Dr. Kreek investigates how genetic factors, as well as drug-induced molecular neurobiological alterations, factor into addictive diseases such as opiate, nicotine, and cocaine addictions, and alcoholism.
Dr. Kreek investigates the biological basis of addictive diseases as well as existing and novel treatments for these conditions. Her lab also researches the medical complications of drug abuse, such as hepatitis C and AIDS, which led her lab to discover in 1984 that the second most common risk group for HIV-1/AIDS is parenteral drug users.
Dr. Kreek’s research focuses on the endogenous opioid system, which modulates stress, pain, and reward, and the roles that specific opioid peptides and their receptors play in normal and abnormal circumstances. Heroin and morphine, as well as cocaine and alcohol, activate these different opiate receptors, directly or indirectly. Dr. Kreek and her colleagues examine gene expression changes in animals that are given or are allowed to self-administer a drug of abuse to study how this exposure impacts the brain’s neurochemistry, neurobiology, and circuitry and to identify targets for potential treatments. The lab also studies epigenetic, physiologic, and behavioral effects of drug administration on the endogenous opioid system and related signaling networks. Microdialysis is performed in rats and mice for dynamic studies of neurotransmitter release and peptide processing in the brain.
The lab studies the roles of the μ and κ opioid receptor systems and the CRF/CRFR1 and vasopressin/V1b receptor systems in alcohol “binge”-like drinking models using rats and inbred strains and genetically modified mice. Additionally, as illicit oxycodone use in adolescence has become a major public health problem, the lab is investigating behavior and neurobiological changes in adolescent versus adult mice during and after self-administration of oxycodone. The lab also is working on the synthesis and study of new chemicals, primarily κ opioid ligands, which could become treatments for specific addictive diseases and co-occurring depression.
Components underlying the neurobiology of addictive diseases are the focus of clinical studies in cocaine- and alcohol-addicted persons and in former heroin addicts in treatment with long-term methadone or buprenorphine-naloxone. Gene polymorphisms that may play a role in addiction or genes that may alter responses to medications (pharmacogenetics) and affect normal physiology (physiogenetics) are identified. Dr. Kreek identified and characterized a functional single-nucleotide polymorphism (A118G) in the μ opioid receptor, which increases vulnerability to develop opioid and alcohol addictions and significantly alters stress responsivity in healthy humans; a mouse model of this variant is currently used in studies.
Dr. Kreek is well known for her pioneering work in the development of methadone maintenance therapy for heroin addiction in the 1960s, a therapy that has been documented to be the most effective treatment for an addiction and now commonly used to treat opiate addiction throughout the world with 1.3 million persons in daily treatment. She also was one of the first to document in 1985 that drugs of abuse significantly alter expression of specific genes in specific brain regions with resultant neurochemical and behavioral changes.
Columbia University College of Physicians and Surgeons
Internship in medicine, 1962–1963
Assistant Residency in medicine, 1963–1964
New York Hospital
Attending Physician, 1971–
Clinical Assistant Professor, 1971–1977
Weill Cornell Medical College
Assistant Professor, 1967–1972
Senior Research Associate, 1972–1983
Associate Professor, 1983–1994
The Rockefeller University
Associate Physician, 1964–1972
Senior Physician, 1994–
The Rockefeller University Hospital
Betty Ford Award, 1996
Specific Recognition Award for Research in the Science of Addiction, Executive Office of the President, 1998
R. Brinkley Smithers Distinguished Scientist Award, 1999
Nathan B. Eddy Memorial Award, 1999
Lifetime Science Award, National Institute on Drug Abuse, 2014
Zhang, Y. et al. Mouse model of the OPRM1 (A118G) polymorphism: differential heroin self-administration behavior compared with wild-type mice. Neuropsychopharmacology. 40, 1091–1100 (2015).
Zhang, Y. et al. Self administration of oxycodone alters synaptic plasticity gene expression in the hippocampus differentially in male adolescent and adult mice. Neuroscience 285, 34–46 (2015).
Levran, O. et al. Stress-related genes and heroin addiction: a role for a functional FKBP5 haplotype. Psychoneuroendocrinology 45, 67–76 (2014).
Yuferov, V. et al. Neurocognitive and neuroinflammatory correlates of PDYN and OPRK1 mRNA expression in the anterior cingulate in postmortem brain of HIV-infected subjects. J Neuroinflammation 11, 5 (2014).
Butelman, E.R. et al. κ-opioid receptor/dynorphin system: genetic and pharmacotherapeutic implications for addiction. Trends Neurosci. 35, 587–596 (2012).