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George Koob, PhD

George Koob, PhD

Please note - Dr. Koob is currently on a leave of absence from UCSD to serve as Director of the National Institute on Alcohol Abuse and Alcoholism in Washington DC

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Dr. Koob's research interests have been 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 (extended amygdala) 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 worldGÇÖs 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.

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

Koob, G.F., Markou, A., Weiss, F. and Schulteis, G., Opponent process and drug dependence: neurobiological mechanisms, Seminars in the Neurosciences, 5 (1993) 351-358.

Koob, G.F., Heinrichs, S.C., Menzaghi, F., Pich, E.M. and Britton, K.T., Corticotropin releasing factor, stress and behavior, Seminars in the Neurosciences, 6 (1994) 221-229.

Koob, G.F., Hedonic valence, dopamine, and motivation, Molecular Psychiatry, 1 (1996) 186-189.

Koob, G.F., Drug addiction: the yin and yang of hedonic homeostasis, Neuron, 16 (1996) 893-896.

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

Koob, G.F., Roberts, A.J., Schulteis, G., Parsons, L.H., Heyser, C.J., Hyytia, P., Merlo-Pich, E. and Weiss, F., Neurocircuitry targets in ethanol reward and dependence, Alcoholism: Clinical and Experimental Research, 22 (1998) 3-9.

Koob, G.F., Sanna, P.P. and Bloom, F.E., Neuroscience of addiction, Neuron, 21 (1998) 467-476.

Koob, G.F. and Heinrichs, S.C., A role for corticotropin-releasing factor and urocortin in behavioral responses to stressors, Brain Research, 848 (1999) 141-152.

Koob, G.F., Stress, corticotropin-releasing factor, and drug addiction. In: C. Sandman, F.L. Strand, B. Beckwith, B. Chronwall, B. Flynn and R.J. Nachman (Eds.), Neuropeptides: Structure and Function in Biology and Behavior (series title: Annals of the New York Academy of Sciences, vol. 897), New York Academy of Sciences, New York, 1999, pp. 27-45.

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

Koob, G.F., Alcoholism: allostasis and beyond, Alcoholism: Clinical and Experimental Research, 27 (2003) 232-243.

Koob, G.F., Neuroadaptive mechanisms of addiction: studies on the extended amygdala, European Neuropsychopharmacology, 13 (2003) 442-452.

Koob, G.F., Drug reward and addiction. In: L.R. Squire, F.E. Bloom, S.K. McConnell, J.L. Roberts, N.C. Spitzer and M.J. Zigmond (Eds.), Fundamental Neuroscience, 2nd edition, Academic Press, San Diego, 2003, pp. 1127-1143.

Koob, G.F., Allostatic view of motivation: implications for psychopathology. In: R.A. Bevins and M.T. Bardo (Eds.), Motivational Factors in the Etiology of Drug Abuse (series title: Nebraska Symposium on Motivation, vol. 50), University of Nebraska Press, Lincoln NE, 2004, pp. 1-18.

Heinrichs, S.C. and Koob, G.F., Corticotropin-releasing factor in brain: a role in activation, arousal, and affect regulation, Journal of Pharmacology and Experimental Therapeutics, 311 (2004) 427-440.

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

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. 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.

Roberto M, Gilpin NW, OGÇÖDell LE, Cruz MT, Morse AC, Siggins GR, Koob GF. Cellular and behavioral interactions of gabapentin with alcohol dependence. Journal of Neuroscience, 2008, 28:5762-5771.

George O, Ghozland S, Azar MR, Cottone P, Zorrilla EP, Parsons LH, OGÇÖDell LE, Richardson HN, Koob GF. CRF-CRF1 system activation mediates withdrawal-induced increases in nicotine self-administration in nicotine-dependent rats. Proceedings of the National Academy of Sciences USA, 2007, 104:17198-17203.

Funk CK, Zorrilla EP, Lee MJ, Rice KC, Koob GF. Corticotropin-releasing factor 1 antagonists selectively reduce ethanol self-administration in ethanol-dependent rats. Biological Psychiatry, 2007, 61:78-86.

Funk CK, O'Dell LE, Crawford EF, Koob GF. Corticotropin-releasing factor within the central nucleus of the amygdala mediates enhanced ethanol self-administration in withdrawn, ethanol-dependent rats. Journal of Neuroscience, 2006, 26:11324-11332.