John C. Crabbe, Ph.D.
Positions
Professor, Behavioral Neuroscience
Senior Research Career Scientist, Research Service, Department of Veterans Affairs Medical Center
Director, Portland Alcohol Research Center
Contact
crabbe@ohsu.edu; Phone: 503-273-5298; Lab Phone: 503-220-8262 Ext 56675; Fax: 503-721-1029; Office: VAMC Bldg 101, Room 601a
Research Interests
mouse behavior genetics; alcohol and drug abuse; genetic animal models; drug dependence; drug tolerance
Major Areas
Pharmacogenetics; tolerance and dependence; gene mapping
Preceptor Rotation and Mentorship Availability
Dr. Crabbe is available for preceptor rotations and/or mentorship for all upcoming academic terms.
Summary of Current Research
I have developed mouse pharmacogenetic models for sensitivity to and dependence on ethanol by selectively breeding lines of mice resistant, or susceptible, to the severity of withdrawal from ethanol dependence. With my collaborators I am analyzing the neurobiological mechanisms underlying the large differences between the Withdrawal Seizure-Prone and -Resistant lines. These studies are concentrated on the neuropharmacological mechanisms leading to alcohol withdrawal convulsions, on their differential susceptibility to other drugs of abuse, and on developing a more comprehensive set of behavioral assays characterizing withdrawal severity.
Other approaches include studies of multiple inbred and recombinant strains of mice examining the basis for genetic correlations between susceptibilities to different drugs of abuse. These studies are exploring 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. Using statistical techniques for mapping Quantitative Trait Loci (QTLs), my collaborators are identifying and mapping specific major and minor genes of importance. We are beginning to identify candidate genes for particular QTLs, and are developing congenic strains by genotypic (marker-based) selection for certain QTLs of pleiotropic importance.
We are also developing new lines of mice selectively bred for binge Drinking in the Dark as a part of the Integrative Neuroscience Initiative on Alcoholism (INIA-West) 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.
Recent Publications
Crabbe, J.C., Cameron, A.J., Munn, E., Bunning, M, Wahlsten, D. (2008) Overview of mouse assays on ethanol intoxication. Curr. Protocols in Neurosci. 9.26.1-9.26.19, January, 2008.
Milner, L.C., Crabbe, J.C. (2008) Three murine anxiety models: results from multiple inbred strains comparisons. Genes Brain Behav. 7:496-505.
Philibin, S.D., Cameron, A.J., Metten, P., Crabbe, J.C. (2008) Motor impairment: a new ethanol withdrawal phenotype in mice. Behav. Pharmacol. 19:604-614.
Belknap, J.K., Metten, P., Beckley, E.H., Crabbe, J.C. (2008) Genetic codetermination of drug abuse liability: multivariate analyses of mouse inbred strain responses to ethanol, morphine, diazepam, and pentobarbital. Trends in Pharmacological Sciences 29:537-543.
Tambour, S., Brown, L.L., Crabbe, J.C. (2008) Gender and age at drinking onset affect voluntary alcohol consumption but neither the alcohol deprivation effect nor response to stress in mice. Alcoholism: Clin. Exper. Res. 32:2100-2106.
Beckley, E.H., Fretwell, A.M., Tanchuck, M.A., Gililland, K.R., Crabbe, J.C., Finn, D.A. (2008) Decreased anticonvulsant efficacy of allopregnanolone during ethanol withdrawal in female Withdrawal Seizure-Prone vs. Withdrawal Seizure-Resistant mice. Neuropsychopharmacol. 54:365-374.
Mulligan, M.K., Ponomarev, I., Boehm, S.L. II, Owen, J.A., Levin, P.S., Blednov, Y.A., Crabbe, J.C., Bergeson, S.E. (2008) Alcohol trait and transcriptional genomic analysis of C57BL/6 substrains. Genes Brain Behav. 7:677-689.
Crabbe, J.C., Metten, P., Rhodes, J.S., Yu, C.H., Brown, L.L., Phillips, T.J., Finn, D.A. (2009) A line of mice selected for high blood alcohol concentrations shows drinking in the dark to intoxication. Biol. Psychiatry 65:662-670
Cozzoli DK, Goulding SP, Zhang PW, Xiao B, Hu JH, Ary AW, Obara I, Rahn A, Abou-Ziab H, Tyrrel B, Marini C, Yoneyama N, Metten P, Snelling C, Dehoff MH, Crabbe JC, Finn DA, Klugmann M, Worley PF, Szumlinski KK. (2009) Binge drinking upregulates accumbens mGluR5-Homer2-PI3K signaling: functional implications for alcoholism. J Neurosci 29:8655-68.
Ehlers, C.L., Walter, N.A.R., Dick, D.M., Buck, K.J., Crabbe, J.C. (2010) A comparison of selected quantitative trait loci associated with alcohol use phenotypes in human and mouse models. Addiction Biology 15:185-199.
Sher, K.J,, Dick, D.M., Crabbe, J.C., Hutchison, K. E., O'Malley, S.S., Heath, A.C. (2010) Consilient research approaches in studying gene x environment interactions in alcohol research. Addiction Biology 15:200-216.
Crabbe, J.C. Bell, R.L., Ehlers, C.L. (2010) Human and laboratory rodent low response to alcohol: Is better consilience possible? Addiction Biology 15:125-144.
Also see Dr. Crabbe's PubMed Listing
Education
B.A. (1968) Stanford University
M.A. (1972) University of Colorado
Ph.D. (1973) University of Colorado
Previous Positions
Research Fellow, Organon International BV, Oss, the Netherlands
Lecturer, University of California
