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

  • "Stable histone methylation changes at proteoglycan network genes following ethanol exposure." Frontiers in Genetics  In: , Vol. 9, No. AUG, 346, 30.08.2018.
  • "Gender-Specific Effects of Selection for Drinking in the Dark on the Network Roles of Coding and Noncoding RNAs." Alcoholism: Clinical and Experimental Research  In: , Vol. 42, No. 8, 01.08.2018, p. 1454-1465.
  • "An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice." Alcohol  In: , Vol. 68, 01.05.2018, p. 19-35.
  • "Genome-Wide Expression Profiles Drive Discovery of Novel Compounds that Reduce Binge Drinking in Mice." Neuropsychopharmacology  In: , Vol. 43, No. 6, 01.05.2018, p. 1257-1266.
  • "Pharmacogenetic Manipulation of the Nucleus Accumbens Alters Binge-Like Alcohol Drinking in Mice." Alcoholism: Clinical and Experimental Research  In: , Vol. 42, No. 5, 01.05.2018, p. 879-888.
  • "Reproducibility and replicability of rodent phenotyping in preclinical studies." Neuroscience and Biobehavioral Reviews  In: , Vol. 87, 01.04.2018, p. 218-232.
  • "Dissecting Brain Networks Underlying Alcohol Binge Drinking Using a Systems Genomics Approach." Molecular Neurobiology  In: , 01.01.2018.
  • "High Drinking in the Dark (HDID) mice are sensitive to the effects of some clinically relevant drugs to reduce binge-like drinking." Pharmacology Biochemistry and Behavior  In: , Vol. 160, 01.09.2017, p. 55-62.
  • "Ethanol withdrawal-induced dysregulation of neurosteroid levels in plasma, cortex, and hippocampus in genetic animal models of high and low withdrawal." Psychopharmacology  In: , 29.06.2017, p. 1-19.
  • "Prefrontal cortex expression of chromatin modifier genes in male WSP and WSR mice changes across ethanol dependence, withdrawal, and abstinence." Alcohol  In: , Vol. 60, 01.05.2017, p. 83-94.
  • "Alignment of the transcriptome with individual variation in animals selectively bred for High Drinking-In-the-Dark (HDID)." Alcohol  In: , Vol. 60, 01.05.2017.
  • "Reproducibility of Experiments with Laboratory Animals : What Should We Do Now?" Alcoholism: Clinical and Experimental Research  In: , Vol. 40, No. 11, 01.11.2016, p. 2305-2308.
  • "Effects of acute alcohol withdrawal on nest building in mice selectively bred for alcohol withdrawal severity." Physiology and Behavior  In: , Vol. 165, 15.10.2016, p. 257-266.
  • "Progress with nonhuman animal models of addiction." Journal of Studies on Alcohol and Drugs  In: , Vol. 77, No. 5, 01.09.2016, p. 696-699.
  • "Fear conditioning in mouse lines genetically selected for binge-like ethanol drinking." Alcohol  In: , Vol. 52, 01.05.2016, p. 25-32.
  • "Nest building is a novel method for indexing severity of alcohol withdrawal in mice." Behavioural Brain Research  In: , Vol. 302, 01.04.2016, p. 182-190.
  • "Neuropeptide Y response to alcohol is altered in nucleus accumbens of mice selectively bred for drinking to intoxication." Behavioural Brain Research  In: , Vol. 302, 01.04.2016, p. 160-170.
  • "Protein kinase C epsilon activity in the nucleus accumbens and central nucleus of the amygdala mediates binge alcohol consumption." Biological Psychiatry  In: , Vol. 79, No. 6, 15.03.2016, p. 443-451.
  • "Corrigendum to Distinct ethanol drinking microstructures in two replicate lines of mice selected for drinking to intoxication [Genes, Brain and Behavior 14, 5, (2015), 398-410] DOI : 10.1111/gbb.12225." Genes, Brain and Behavior  In: , Vol. 15, No. 3, 01.03.2016, p. 356.
  • "Gene Targeting Studies of Hyperexcitability and Affective States of Alcohol Withdrawal in Rodents." International Review of Neurobiology  In: , 2016.
  • "Commonalities and Distinctions Among Mechanisms of Addiction to Alcohol and Other Drugs." Alcoholism: Clinical and Experimental Research  In: , Vol. 39, No. 10, 01.10.2015, p. 1863-1877.
  • "Distinct ethanol drinking microstructures in two replicate lines of mice selected for drinking to intoxication." Genes, Brain and Behavior  In: , Vol. 14, No. 5, 01.06.2015, p. 398-410.
  • "Genotypic and sex differences in anxiety-like behavior and alcohol-induced anxiolysis in High Drinking in the Dark selected mice." Alcohol  In: , Vol. 49, No. 1, 01.02.2015, p. 29-36.
  • "Rewarding and aversive effects of ethanol in High Drinking in the Dark selectively bred mice." Addiction Biology  In: , Vol. 20, No. 1, 01.01.2015, p. 80-90.
  • "Dual-Trait Selection for Ethanol Consumption and Withdrawal : Genetic and Transcriptional Network Effects." Alcoholism: Clinical and Experimental Research  In: , Vol. 38, No. 12, 01.12.2014, p. 2915-2924.
  • "Addiction."   Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease: Fifth Edition. Elsevier Inc., 2014. p. 1321-1329.
  • "Experimenter effects on behavioral test scores of eight inbred mouse strains under the influence of ethanol." Behavioural Brain Research  In: , Vol. 272, 01.10.2014, p. 46-54.
  • "Quantification of ten neuroactive steroids in plasma in Withdrawal Seizure-Prone and -Resistant mice during chronic ethanol withdrawal." Psychopharmacology  In: , Vol. 231, No. 17, 01.09.2014, p. 3401-3414.
  • "Neurobiology of Alcohol Dependence."   Elsevier Inc., 2014. 560 p.
  • "Progress in a replicated selection for elevated blood ethanol concentrations in HDID mice." Genes, Brain and Behavior  In: , Vol. 13, No. 2, 02.2014, p. 236-246.

Additional information

Edit profile