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Department of Neuroscience


Olivier George, Ph.D.

Associate Professor
CoDirector ARC Animal Core
Department of Neuroscience
California Campus
Laboratory Website
ogeorge@scripps.edu
(858) 784-9039

Scripps Research Joint Appointments

Faculty, Graduate Program

Research Focus

Olivier George has a major interest in the brain stress and cognitive systems in drug addiction. The main goals of his lab are to unveil the neurobiological mechanisms underlying the transition to drug addiction, and to develop novel pharmacological and non-pharmacological treatments to reduce compulsive drug seeking and taking. Dr George and his team have identified that activation of the CRF system in the extended amygdala and prefrontal cortex during withdrawal mediates excessive nicotine and alcohol intake. He has also demonstrated that escalation of cocaine, methamphetamine and alcohol intake produces a dysfunction of the prefrontal cortex leading to cognitive impairment. Dr. George has also pioneered the development of two novel animal models of escalation of nicotine intake and exposure to electronic cigarette. Current studies are exploring the role of the CRF, dynorphin, hypocretin and steroid systems in addiction to alcohol, nicotine, cocaine and prescription opiates. Dr. George is also CoDirector of the Animal Models/Biochemical Core of the TSRI-Alcohol Research Center and his work is funded by NIAAA and NIDA.

Education

Ph.D., Neuroscience and Neuropharmacology, University of Bordeaux, France, 2004

Professional Experience

2016-present: Associate Professor / Co-director Alcohol Research Center - Animal Core 
2013-2016: Assistant Professor / Co-director Alcohol Research Center - Animal Core
2011-2013: Senior Staff Scientist / Co-director Alcohol Research Center - Animal Core 
2009-2010: Staff Scientist / Co-director Lab. of Neuropharmacology and Alcohol Research Center - Animal Core
2008-2009: Senior Research Associate
2006-2007: Research Associate Laboratory of Neuropharmacology. The Scripps Research Institute, La Jolla CA, USA.
2004-2006: Postdoctoral Fellow Bordeaux Neuroscience Institute, Inserm, Piazza lab, Bordeaux, France.
2001-2004: Graduate Student University of Bordeaux II, Le Moal lab, Bordeaux, France.

Selected References

Peer-Reviewed Articles

  1. Cortical and amygdalar neuronal ensembles of alcohol seeking, drinking and withdrawal. Hope B and George O. Neuropharmacology. In press
  2. Deletion of α5 nicotine receptor subunits abolishes nicotinic aversive motivational effects in a manner that phenocopies dopamine receptor antagonism. Grieder TR, George O, Bergamini M, Yee M, Chwalek M, Maal-Bared G, Wargas-Perez H, van der Kooy D. European Journal of Neuroscience. 2017, in press.
  3. Nicotine vapor method to induce nicotine dependence in rodent. Kallupi M and George O. Current Protocols in Neuroscience. 2017, in press.
  4. Alcohol dependence disrupts amygdalar L-type voltage-gated calcium channel mechanisms. Varodayan FP, de Guglielmo G, Logrip ML, George O, Roberto M. Journal of Neuroscience. 2017 Mar 31. pii: 3721-16. doi: 10.1523/JNEUROSCI.3721-16.2017. PMID: 28363981.
  5. Voluntary induction and maintenance of alcohol dependence in rats using alcohol vapor self-administration. de Guglielmo G, Kallupi M, Cole MD, George O. Psychopharmacology (Berl). 2017 Mar 24. doi: 10.1007/s00213-017-4608-7. PMID: 28342089.
  6. High-frequency stimulation of the subthalamic nucleus blocks compulsive-like re-escalation of heroin taking in rats. Wade C, Kallupi M, Hernandez D, Breysse E, de Guglielmo G, Crawford E, Koob G, Schweitzer P, Baunez, George O. Neuropsychopharmacology 2016; doi: 10.1038/npp.2016.270
  7. Genetic and pharmacologic manipulation of TLR4 has minimal impact on ethanol consumption in rodents. Harris RA, Bajo M, Bell RL, Blednov YA, Varodayan FP, Truitt J, de Guglielmo G, Lasek AW, Logrip ML, Vendruscolo LF, Roberts AJ, Roberts E, George O, Mayfield J, Billiar TR, Hackam DJ, Mayfield RD, Koob GF, Roberto M, Homanics GE. Journal of neuroscience. 2016 Dec 16. pii: 2002-16. PMID: 27986929.
  8. Recruitment of a neuronal ensemble in the central nucleus of the amygdala is required for alcohol dependence. de Guglielmo G, Crawford E, Kim S, Vendruscolo L, Hope B, Brennan M, Cole M, Koob G, and George O. Journal of neuroscience 2016. 36 (36), 9446-9453
  9. A Transgenic Rat for Investigating the Anatomy and Function of Corticotrophin Releasing Factor Circuits. Pomrenze MB, Millan EZ, Hopf FW, Keiflin R, Maiya R, Blasio A, Dadgar J, Kharazia V, De Guglielmo G, Crawford E, Janak PH, George O, Rice KC, Messing RO. Frontiers in Neuroscience 2015; 9:487. PMID:26733798.
  10. Glucocorticoid receptor antagonism decreases alcohol seeking in alcohol-dependent individuals. Vendruscolo LF, Estey D, Goodell V, Macshane LG, Logrip ML, Schlosburg JE, McGinn MA, Zamora-Martinez ER, Belanoff JK, Hunt HJ, Sanna PP, George O, Koob GF, Edwards S, Mason BJ. J Clin Invest. 2015 Aug 3;125(8):3193-7. PMID: 26121746.
  11. Chronic nicotine activates stress/reward-related brain regions and facilitates the transition to compulsive alcohol drinking. Leão RM, Cruz FC, Vendruscolo LF, de Guglielmo G, Logrip ML, Planeta1 CS, Hope BT, Koob GF, George O. Journal of neuroscience 2015; 35(15):6241-53. PMID: 25878294.
  12. Increased CRF signaling in a ventral tegmental area-interpeduncular nucleus-medial habenula circuit induces anxiety during nicotine withdrawal. Zhao-Shea R, DeGroot S, Liu L, Vallaster M, Pang X, Su Q, Gao G, Rando O, Martin G, George O, Gardner P, Tapper A. Nature Communication 2015; 6:6770. NIHMSID: NIHMS667783 PMID: 25898242.
  13. Kappa Opioid Receptors in the Nucleus Accumbens Shell Mediate Escalation of Methamphetamine Intake. Whitfield T, Schlosburg JE, Wee S, Gould A, George O, Grant Y, Martinez E, Crawford E, Edwards S, Vendruscolo L, Koob G. Journal of neuroscience 2015; 35(10):4296-305. PMID: 25762676.
  14. VTA CRF neurons mediate the aversive effects of nicotine withdrawal and promote intake escalation. Grieder TE, Herman MA, Contet C, Tan LA, Vargas-Perez H, Cohen A, Chwalek M, Maal-BaredG, Freiling J, Schlosburg JE, Clarke L, Crawford E, Koebel P, Canonigo V, Sanna PP, Tapper AR, Roberto M, Kieffer BL, Sawchenko PE, Koob GF, van der Kooy D, George O. Nature Neuroscience. 2014; NIHMS636720, PMID: 25402857.
  15. Extended access nicotine self-administration with periodic deprivation increases immature neurons in the hippocampus. Cohen A, Soleiman MT, Talia R, Koob GF, George O and Mandyam CD. Psychopharmacology. 2014; 20(1):56-68. NIHMSID: NIHMS502230, PMID: 23869743.
  16. Gene expression changes consistent with neuroAIDS and impaired working memory in HIV-1 transgenic rats. Repunte-Canonigo V, Lefebvre, George O, Kawamura T, Morales M, Koob G, Califano A, Masliah E and Sanna PP. Molecular Neurodegeneration. 2014; 9:26. PMID: 24980976.
  17. Negative reinforcement via motivational withdrawal is the driving force behind the transition to addiction. George O, Koob G, Vendruscolo L. Psychopharmacology. 2014; 231(19):3911-7. PMID: 24923982
  18. Anticipatory 50kHz ultrasonic vocalizations are associated with escalated alcohol intake in dependent rats. Buck CL, Malavar JC, George O, Koob GF, Vendruscolo LF. Behavioral Brain Research. 2014; 271:171-6. NIHMS639034 PMID: 24914463.
  19. Virus-Mediated shRNA Knockdown of Prodynorphin in the Rat Nucleus Accumbens Attenuates Depression-Like Behavior and Cocaine Locomotor Sensitization. Cohen A, Whitfield TW, Kreifeldt M, Koebel P, Kieffer BL, Contet C, George O, Koob GF. PLoS One. 2014; 9(5):e97216. PMID: 24816773.
  20. Nicotine Vapor Inhalation Escalates Nicotine Self-Administration. Gilpin N, Whitaker A, Baynes B, Abdel A, Weil M, George O. Addiction Biology. 2014;19(4):587-92. NIHMS699081 PMID: 23240929.
  21. Hippocampal neurogenesis protects against cocaine-primed relapse. Deschaux O, Vendruscolo L, Schlosburg J, Diaz-Aguilar L, Yuan CJ, Sobieraj JC, George O, Koob GF, and Mandyam CD. Addiction Biology. 2014; 19(4):562-74. NIHMS:423885 PMID:23278919.
  22. Long-term antagonism of kappa opioid receptors prevents escalation of and increased motivation for heroin intake. Schlosburg J, Whitfield TJ. Park P, Crawford E, George O, Vendruscolo L, Koob G. Journal of Neuroscience. 2013; 33(49):19384-92. PMID: 24305833.
  23. Dopamine D1 and mu-opioid receptor antagonism blocks anticipatory 50 kHz ultrasonic vocalizations induced by palatable food cues in Wistar rats. Buck CL, Vendruscolo LF, Koob GF, George O. Psychopharmacology. 2013; 231(5):929-37. NIHMS539967 PMID: 24221826, PMCID: PMC3945412
  24. Extended access to nicotine leads to a CRF(1) receptor dependent increase in anxiety-like behavior and hyperalgesia in rats. Cohen A, Treweek J, Edwards S, Leão RM, Schulteis G, Koob GF, George O.  Addiction Biology. 2013 Jul 22. doi: 10.1111/adb.12077. PMID: 23869743.
  25. Animal models of nicotine exposure: relevance to second-hand smoking, electronic cigarette use, and compulsive smoking. Cohen A, George O. Frontiers in Psychiatry. 2013; 4:41. PubMed [journal] PMID: 23761766.
  26. Addiction as a stress surfeit disorder. Koob GF, Buck CL, Cohen A, Edwards S, Park PE, Schlosburg JE, Schmeichel B, Vendruscolo LF, Wade CL, Whitfield TW Jr, George O.  Neuropharmacology. 2014; 76 Pt B:370-82. NIHMS502140 PMID: 23747571.
  27. Neuropeptide Y Y(2) R blockade in the central amygdala reduces anxiety-like behavior but not alcohol drinking in alcohol-dependent rats. Kallupi M, Vendruscolo LF, Carmichael CY, George O, Koob GF, Gilpin NW. Addiction Biology. 2013; 19(5):755-7. NIHMS476832 PMID: 23639035.
  28.  Control of craving by the prefrontal cortex. George O, Koob GF. Proceedings of the National Academy of Science (PNAS) U S A. 2013; 110(11):4165-6. PMID: 23483010.
  29. Recruitment of medial prefrontal cortex neurons during alcohol withdrawal predicts cognitive impairment and excessive alcohol drinking. George O, Sanders C, Freiling J, Grigoryan E, Vu S, Allen CD, Crawford E, Mandyam CD, Koob GF. Proceedings of the National Academy of Science (PNAS) U S A. 2012 Oct 30;109(44):18156-61. doi: 10.1073/pnas.1116523109. PubMed PMID: 23071333.
  30. Robust escalation of nicotine intake in extended access to nicotine self-administration with intermittent periods of abstinence. Cohen A, Koob GF, George O. Neuropsychopharmacology. 2012 Aug;37(9):2153-60. doi: 10.1038/npp.2012.67. PMID: 22549121.
  31. Effects of the specific alpha4beta2 nAChR antagonist, 2-fluoro-3-(4-nitrophenyl) deschloroepibatidine, on nicotine reward-related behaviors in rats and mice. Tobey K, Walentiny D, Wiley J, Carroll F, Damaj MI, Azar M, Koob G, George O, Harris L, Vann R. Psychopharmacology (Berl). 2012 Sep;223(2):159-68. doi: 10.1007/s00213-012-2703-3. Epub 2012 Apr 22
  32. Effects of the combination of metyrapone and oxazepam on intravenous nicotine self-administration in rats. Goeders NE, Cohen A, Fox BS, Azar MR, George O, Koob GF. Psychopharmacology (Berl). 2012 Mar 15
  33. Phasic D1 and tonic D2 dopamine signaling double dissociate the motivational effects of acute nicotine and chronic nicotine withdrawal. Grieder TE, George O, Tan H, George SR, Le Foll B, Laviolette SR, van der Kooy D. Proceedings of the National Academy of Science (PNAS)U S A. 2012; 109(8):3101-6. PMID: 22308372.
  34. Allostasis and Addiction: Role of the Dopamine and Corticotropin-Releasing Factor Systems. George O, Le Moal M, Koob GF. Physiology and Behavior. 2012 Apr 12;106(1):58-64.
  35. Levels of neural progenitors in the hippocampus predicts memory impairments and relapse to drug seeking as a function of excessive methamphetamine self-administration Recinto P, Samant ARH, Chavez G, Kim A, Yuan CJ, Soleiman M, Grant Y, Edwards S, Wee S, Koob GF, George O, Mandyam CD. Neuropsychopharmacology 2012 Apr;37(5):1275-87.
  36. Craving, context and the cortex. George O, Koob GF. Nature Neuroscience. 2011 Apr;14(4):409-10.
  37. Varenicline blocks nicotine intake in rats with extended access to nicotine self-administration. George O, Lloyd A, Carroll FI, Damaj MI, Koob GF. Psychoharmacology. 2011; 213(4):715-22. NIHMS253291 PMID: 20924754.
  38. Exposure to chronic intermittent nicotine vapor induces nicotine dependence. George O, Grieder TE, Cole M, Koob GF. Pharmacology Biochemistry & Behavior. 2010 Jul; 96(1):104-7. Epub 2010 Apr 24.
  39. Individual differences in prefrontal cortex function and the transition from drug use to drug dependence. George O, Koob GF. Neuroscience Biobehavioral Review. 2010; 35(2):232-47. PMID:20493211.
  40. Low Brain Allopregnanolone Levels Mediate Flattened Circadian Activity Associated with Memory Impairments in Aged Rats. George O, Vallée M, Vitiello S, Moal ML, Piazza PV, Mayo W. Biological Psychiatry. 2010; 68(10):956-63. NIHMS193516 PMID: 20471631.
  41. A role for the endocannabinoid system in the increased motivation for cocaine in extended-access conditions. Orio L, Edwards S, George O, Parsons LH, Koob GF. Journal of Neuroscience. 2009 Apr 15;29(15):4846-57.
  42. Extended Access to Cocaine Self-Administration Produces Long-Lasting Prefrontal Cortex-Dependent Working Memory Impairments. George O, Mandyam CD, Wee S and Koob GF. Neuropsychopharmacology. 2008, (33), 2474-2482
  43. CRF-CRF1 system activation mediates withdrawal-induced increases in nicotine self-administration in nicotine dependent rats. George O, Ghozland S, Azar M, Zorrilla E, Parsons L,’Dell L, Richardson H, Koob GF. Proceedings of the National Academy of Science (PNAS) U S A. 2007; 104(43):17198-203. PMID:17921249.
  44. Smad-dependent alterations of PPT cholinergic neurons as a pathophysiological mechanism of age-associated sleep-dependent memory impairments. George O, Parducz A, Dupret D, Le Moal M, Piazza PV, Mayo W. Neurobiology of Aging 2006 Dec 27(12):1848-58.
  45. Chronic exposure of rats to noise: Relationship between long-term memory deficits and slow wave sleep disturbances. Rabat A, Bouyer JJ, George O, Le Moal M, Mayo W. Behavioral Brain Research. 2006 Aug, 171(2):303-12.
  46. Neurosteroids and Cholinergic Systems: implication for sleep and memory processes and potential role for age-related psychiatric alterations. George O, Vallée M, Le Moal M, Mayo W. Psychopharmacology 2006 Jun, 186(3):402-13.
  47. Motherhood-induced memory improvement persists across lifespan but is abolished by a gestational stress. Lemaire V, Billard J, Dutar P, George O, Piazza PV, Le Moal M, Mayo W. European Journal of Neuroscience. 2006 Jun 23(12):3368-74.
  48. Sleep-wake states and cortical synchronization control by pregnenolone sulfate into the pedunculopontine nucleus. Darbra S*, George O*, Bouyer JJ, Piazza PV, Le Moal M, Mayo W. Journal of Neuroscience Research. 2004 Jun 76(5):742-7 *: these authors contributed equally to this work.
  49. New insights into the role of neuroactive steroids in cognitive aging. Vallée M, George O, Vitiello S, Le Moal M, Mayo W. Experimental Gerontology 2004 Nov(11-12):1695-704.
  50. Individual differences in cognitive aging: implication of pregnenolone sulfate. Mayo W, George O, Darbra S, Bouyer JJ, Vallee M, Darnaudery M, Pallares M, Lemaire-Mayo V, Le Moal M, Piazza PV, Abrous N. Progress in Neurobiology. 2003 Sep; 71(1):43-8
  51. Book chapter (1) Overview of nicotine withdrawal and negative Reinforcement (Preclinical). George O and Koob GF. In Negative Affective States and Cognitive Impairments in Nicotine Dependence. Editors F. Scott Hall, Jared W. Young, Andre Der-Avakian. Academic Press, 2016. ISBN 0128026693, 9780128026694

 

Links

George Lab

Cocaine Biobank