Scripps Research Logo

George Koob, Ph.D.

Committee Chairman
On leave of absence to direct the National Institute on Alcohol Abuse and
Alcoholism at the National Institutes of Health
Committee On The Neurobiology Of Addictive Disorders
California Campus
Laboratory Website

Research Focus

Research Description

Dr. Koob's  early research interests were directed at the neurobiology of emotion, with a focus on the theoretical constructs of reward and stress. He has made contributions to our understanding of the anatomical connections of the emotional systems and the neurochemistry of emotional function. Dr. Koob has identified afferent and efferent connections of the basal forebrain in the region of the nucleus accumbens, bed nucleus of the stria terminalis, and central nucleus of the amygdala in motor activation, reinforcement mechanisms, behavioral responses to stress, drug self-administration, and the neuroadaptation associated with drug dependence. Dr. Koob's work with the neurobiology of stress includes the characterization of behavioral functions in the central nervous system for catecholamines, opioid peptides, and corticotropin-releasing factor. Corticotropin-releasing factor, in addition to its classical hormonal functions in the hypothalamic-pituitary-adrenal axis, is also located in extrahypothalamic brain structures and may have an important role in brain emotional function. Recent use of specific corticotropin-releasing factor antagonists suggests that endogenous brain corticotropin-releasing factor may be involved in specific behavioral responses to stress, the psychopathology of anxiety and affective disorders, and drug addiction. Dr. Koob also has characterized functional roles for other stress-related neurotransmitters/neuroregulators such as norepinephrine, vasopressin, hypocretin (orexin), neuropeptide Y, and neuroactive steroids.

Dr. Koob also is one of the world’s authorities on the neurobiology of drug addiction. He has contributed to our understanding of the neurocircuitry associated with the acute reinforcing effects of drugs of abuse and more recently on the neuroadaptations of these reward circuits associated with the transition to dependence. He has validated key animal models for dependence associated with drugs of abuse and has begun to explore a key role of anti-reward systems in the development of dependence. The identification of specific neurochemical systems within the basal forebrain system of the extended amygdala involved in motivation has significant theoretical and heuristic impact. From a theoretical perspective, identification of a role for dopaminergic, opioidergic, GABAergic, glutamatergic and corticotropin-releasing factor systems in the excessive drug taking provides a neuropharmacologic basis for the allostatic changes hypothesized to drive the process of pathology associated with addiction, anxiety, and depression. From a heuristic perspective, these findings provide a framework for further molecular, cellular and neurocircuit research that will identify the basis for individual differences in vulnerability to pathology.

Future research plans

Future research is focused on understanding the neurobiological bases for altered motivational states associated with drug addiction at the neurocircuitry, cellular and molecular level and using these studies as a heuristic approach to the study of emotions. The ultimate goal is to understand how cellular and molecular changes produce changes in particular neurocircuits to convey negative emotional states that contribute to the motivation to seek drugs, but also contribute to other disorders of motivation in psychopathology. In addition, the laboratory will be exploring the relationship between pain and emotional systems in the context of the same neurocircuitry. The neurocircuitry under study involves specific elements of the basal forebrain involving the central nucleus of the amygdala, bed nucleus of the stria terminalis and elements of the ventral striatum including the shell and core of the nucleus accumbens. Neuropeptides of the brain stress systems outside of the hypothalamic-pituitary-adrenal system are hypothesized to have a key role in mediating changes in emotional state and include corticotropin releasing factor, dynorphin, vasopressin, substance P,  orexin and neuropeptide Y and nociceptin. Future studies will include identification of molecular factors that load such circuits and neurotransmitter system function, identification of cellular interactions between such brain stress systems and identification of the role of outputs such as the hypothalamus in expressing such negative emotional states. Such research will provide key information not only about the neurobiology of addiction, pain and stress but also key information about the neurobiology of motivational systems in general.

Education

Ph.D., Behavioral Psychology, Johns Hopkins University, 1972
B.S., Zoology, Johns Hopkins University, 1969

Professional Experience

2006-present Professor and Chair, Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute.
1995-Present Director, Alcohol Research Center, The Scripps Research Institute.
1990-2006 Professor, Molecular and Integrative Neurosciences Department (formerly the Department of Neuropharmacology), The Scripps Research Institute.
1983-1989 Associate Member (with tenure), Division of Preclinical Neuroscience and Endocrinology, The Scripps Research Institute.
1977-1983 Staff Scientist, Arthur Vining Davis Center for Behavioral Neurobiology, The Salk Institute for Biological Studies.
1975-1977 Postdoctoral Fellow with Dr. Susan D. Iversen, University of Cambridge, Department of Experimental Psychology, Medical Research Council, Neurochemical Pharmacology Unit. Studies in: catecholamines and behavior.
1972-1975 Staff Scientist, Department of Neurophysiology, Walter Reed Army Institute of Research. Studies in: brain lesions, brain stimulation, behavior, neurochemistry, psychopharmacology.
1969-1972 Predoctoral Fellow, Johns Hopkins University, Department of Environmental Medicine. Training in: physiology, behavior, neurochemistry, environmental physiology.
1965-1969 Undergraduate, Pennsylvania State University, Training in: zoology and psychology.

Awards & Professional Activities

Phi Sigma Society

Alpha Zeta Fraternity


Outstanding Faculty Teaching Award
, Revelle College, University of California, San Diego (1988)

Outstanding Faculty Teaching Award
, Muir College, University of California, San Diego (1989)

Outstanding Faculty Teaching Award
, Warren College, University of California, San Diego (1992, 1993, 1995)

Daniel H. Efron Award
, Excellence in Research in Neuropsychopharmacology, American College of Neuropsychopharmacology (1991)

Highly Cited Researcher
, Institute for Scientific Information (2001)

Distinguished Investigator Award
, Research Society on Alcoholism (2002)

ASAM Annual Award
, American Society of Addiction Medicine (2002)

Tharp Award
, James H. Tharp Trust Committee, Research Society on Alcoholism (2002)

Most Valuable Professor
, Muir College, University of California, San Diego (2004)

Mark Keller Award
, National Institute on Alcohol Abuse and Alcoholism (2004)

Faculty Excellence Award
, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego (2006)

Honorary Doctorate of Science
, Pennsylvania State University (2009)

Outstanding UCSD Professor Award
, Panhellenic Council, University of California, San Diego (2010)

Selected References

Koob, G.F., Drugs of abuse: anatomy, pharmacology and function of reward pathways, Trends in Pharmacological Sciences, 13 (1992) 177-184.

Koob, G.F. and Le Moal, M., Drug abuse: hedonic homeostatic dysregulation, Science, 278 (1997) 52-58.

Koob, G.F. and Le Moal, M., Drug addiction, dysregulation of reward, and allostasis, Neuropsychopharmacology, 24 (2001) 97-129.

Koob, G.F. and Le Moal, M., Plasticity of reward neurocircuitry and the ‘dark side’ of drug addiction, Nature Neuroscience, 8 (2005) 1442-1444.

Heilig M, Koob GF. A key role for corticotropin-releasing factor in alcohol dependence. Trends in Neurosciences, 2007, 30:399-406.

Koob GF, Le Moal M. Addiction and the brain antireward system. Annual Review of Psychology, 2008, 59:29-53.

Koob GF. A role for brain stress systems in addiction. Neuron, 2008, 59:11-34.

Koob GF, Le Moal M. Neurobiological mechanisms for opponent motivational processes in addiction. Philosophical Transactions of the Royal Society B Biological Sciences, 2008, 363:3113-3123.

Koob GF, Lloyd GK, Mason BJ. Development of pharmacotherapies for drug addiction: a Rosetta Stone approach. Nature Reviews Drug Discovery, 2009, 8:500-515.

Koob GF, Le Moal M. Neurobiology of Addiction [ISBN: 0124192394]. Academic Press, London, 2006.

Links

Committee on the Neurobiology of Addictive Disorders

Pearson Center for Alcoholism and Addiction Research

Integrative Neuroscience Initiative on Alcoholism-West

The Scripps Research Institute Alcohol Research Center

Community of Science (Researcher Profile)

University of California, San Diego, Neurosciences Graduate Program