Photo of John C. Crabbe, Ph.D.

John C. Crabbe Ph.D.

  • (503) 273-5298
    • Professor of Behavioral Neuroscience School of Medicine
    • Senior Research Career Scientist, VA Portland Health Care System
    • Behavioral Neuroscience Graduate Program School of Medicine

I have developed mouse pharmacogenetic models for dependence on ethanol by selectively breeding lines of mice resistant, or susceptible, to the severity of withdrawal from ethanol dependence. We have developed a more comprehensive set of behavioral assays characterizing withdrawal severity. With my collaborators we are analyzing the genomic changes underlying the large differences between the Withdrawal Seizure-Prone and -Resistant lines. 

Other approaches include studies of multiple inbred strains of mice examining the basis for genetic correlations between susceptibilities to different effects of ethanol and different drugs of abuse. These studies have explored the specificity of genetic influences across different environments, including multiple laboratories. They are also intended to elucidate gene-environment interactions. Strain patterns of sensitivity sometimes indicate the important influence of single genes on drug responses.

We have also developed new lines of mice selectively bred for binge Drinking in the Dark as a part of the Integrative Neuroscience Initiative on Alcoholism (INIA-Neuroimmune) consortium. These mice drink to the point of intoxication, reaching average blood levels higher than the legal driving limit. We are exploring the pharmacological characteristics of the neural circuitry underlying this drinking as well as the behavioral characteristics of these mice.  We are using these mice as a model for testing novel drugs that could ameliorate drinking and we are exploring their use in informatics-driven genomics studies.

Previous positions
Research Fellow, Organon International BV, Oss, the Netherlands
Lecturer, University of California

Areas of interest

  • Mouse behavior
  • Genetics
  • Alcohol and drug abuse
  • Genetic animal models
  • Binge drinking
  • Drug dependence
  • Drug tolerance

Education

  • B.A., Stanford University 1968
  • M.A., University of Colorado 1972
  • Ph.D., University of Colorado 1973

Honors and awards

  • 2016 Erwin Lecturer Skaggs Sch Pharm UC Denver
  • 2015 Dist Lect Creighton U SoM
  • 2015 Marlatt Mentorship Res Soc Alcoholism
  • 2015 Dist Service Int Behav/Neural Genet Soc
  • 2014 Dist Lect Addiction Res UTMB Galveston TX
  • 2012 Dist Lect Behav Pharmacol Dept Pharmacol/Tox U Toronto
  • 2012 Seixas Dist Service RSA
  • 2011 Keller Honorary Lect NIAAA NIH
  • 2008 Dist Scientist IBANGS
  • 2008 Marsh Lect Texas Tech U So Pharm
  • 2006 Resko Fac Res Achievement/Mentoring OHSU SoM
  • 2005 Middleton outstanding achievement biomed/behav res Dept Vets Affairs Wash DC
  • 2004 Bowles Lect Ctr Alcohol Studies UNC Chapel Hill NC
  • 1998 Isaacson Fdn for Prevent Chem Depend Disease
  • 1996 Dist Res RSA
  • 1995 Discovery Outstanding Med Res Scientist OHSU Foundation
  • 1991 Kendall VA Res Portland VAMC

Memberships and associations

  • Research Society on Alcoholism (1979 – present) Society for Neuroscience (1972 – present) International Society for Biomedical Research on Alcoholism (1982 – present) International Behavioural and Neural Genetics Society (President, 2002-2003) (1996 – present) Behavior Genetics Association (1970 – present) American Association for the Advancement of Science (1979-present)

Publications

Selected publications

  • Crabbe JC et al (1994) Science 264:1715. Crabbe et al (1996) Nature Genetics 14:98. Crabbe et al (1999) Science 284:1670. Rhodes JS et al (2005). Physiol. Behav. 84:53. Kliethermes CL, Crabbe JC (2006) PNASUSA. 103: 5018. Wahlsten D et al (2006). PNASUSA 103:16364. Kendler KS et al (2012) Molec. Psychiat.,17:1306. Iancu OD et al (2013) Alcohol Clin Exp Res 7:1295 Crabbe et al (2014) Genes Brain Behav. 13:236.  Ferguson LB et al (2018) Neuropsychopharmacology 43:1257.

Publications

  • "Experimenter effects on behavioral test scores of eight inbred mouse strains under the influence of ethanol" Behavioural Brain Research October 1 2014
  • "Genetic correlations among inbred strain sensitivities to convulsions induced by 9 convulsant drugs" Brain Research August 27 1990
  • "Human and laboratory rodent low response to alcohol" Addiction Biology April 2010
  • "Pharmacogenetic tools in the study of drug tolerance and dependence" Alcohol  1980
  • "Ethanol preference in homozygous diabetes insipidus (Brattleboro) rats" Annals of the New York Academy of Sciences  1982
  • "Molecular forms and anterior pituitary content of ACTH, β-lipotropin, and β-endorphin in diabetes insipidus di/di (Brattleboro) rats" Annals of the New York Academy of Sciences  1982
  • "Assessment of genetic susceptibility to ethanol intoxication in mice" Proceedings of the National Academy of Sciences of the United States of America March 4 2003
  • "Internet resources for genomic, bioinformatics, and medical genetics information." Current protocols in neuroscience / editorial board, Jacqueline N. Crawley ... [et al.] May 2003
  • "Erratum" Genes, Brain and Behavior August 2004
  • "Ethanol up-regulates nucleus accumbens neuronal activity dependent pentraxin (Narp)" Alcohol June 2012
  • "Transgenic over expression of nicotinic receptor alpha 5, alpha 3, and beta 4 subunit genes reduces ethanol intake in mice" Alcohol May 2012
  • "Characterization of acute functional tolerance to the hypnotic effects of ethanol in mice" Alcoholism: Clinical and Experimental Research July 2004
  • "Acute neuroactive steroid withdrawal in withdrawal seizure-prone and withdrawal seizure-resistant mice" Pharmacology Biochemistry and Behavior  2000
  • "Alcohol and genetics" American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics December 8 2002
  • "Mapping genes that regulate density of dopamine transporters and correlated behaviors in recombinant inbred mice" Journal of Pharmacology and Experimental Therapeutics  2001
  • "How should addiction-related research at the national institutes of health be reorganized?" Frontiers in Psychiatry  2011
  • "Molecular Profiles of Drinking Alcohol to Intoxication in C57BL/6J Mice" Alcoholism: Clinical and Experimental Research April 2011
  • "Tolerance to ethanol and severity of withdrawal in mice are enhanced by a vasopressin fragment" European Journal of Pharmacology May 30 1980
  • "DNA" Psychological Bulletin November 2000
  • "Overview of mouse assays of ethanol intoxication" Current protocols in neuroscience / editorial board, Jacqueline N. Crawley ... [et al.]  2008
  • "Research Psychologists' Roles in the Genetic Revolution" American Psychologist April 2003
  • "Gene expression induced by drugs of abuse" Current Opinion in Pharmacology February 2005
  • "Effects of genetic and procedural variation on measurement of alcohol sensitivity in mouse inbred strains" Behavior Genetics July 2006
  • "Vasopressin and ethanol preference. I. Effects of vasopressin and the fragment DGAVP on altered ethanol preference in Brattleboro diabetes insipidus rats" Peptides  1985
  • "The Influence of Selection for Ethanol Withdrawal Severity on Traits Associated With Ethanol Self-Administration and Reinforcement" Alcoholism: Clinical and Experimental Research February 2011
  • "Genetic correlations with ethanol withdrawal severity" Pharmacology Biochemistry and Behavior  1983
  • "Temperature regulation in mice during withdrawal from ethanol dependence" American Journal of Physiology - Renal Fluid and Electrolyte Physiology  1994
  • "Congenic Mapping of Alcohol and Pentobarbital Withdrawal Liability Loci to a " Journal of Neuroscience May 1 2002
  • "Alcohol and genetics" Trends in Molecular Medicine July 1 1999
  • "NMDA receptor subunit mRNA and protein expression in ethanol-withdrawal seizure-prone and -resistant mice" Alcoholism: Clinical and Experimental Research May 2001

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