Graduate Studies Faculty
John C. Crabbe, Ph.D.
Research Interests:mouse behavior genetics; alcohol and drug abuse; genetic animal models; binge drinking; drug dependence; drug tolerance » PubMed Listing
Preceptor RotationsAcademic Term Available Winter 2016 Maybe Spring 2016 Maybe Summer 2017 Maybe Fall 2017 Maybe Winter 2017 Maybe Spring 2017 Maybe
Faculty MentorshipDr. Crabbe might be available as a mentor for 2016-2017. Dr. Crabbe might be available as a mentor for 2017-2018.
Pharmacogenetics; tolerance and dependence; gene mapping
Summary of Current Research
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. 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 genetic and 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 strains of mice examining the basis for genetic correlations between susceptibilities to effects of 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 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 as well as the behavioral characteristics of these mice.
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 Psychiat 65:662-670
Ehlers, C., Walter, N., Dick, D., Buck, K., Crabbe, J. (2010) A comparison of selected quantitative trait loci associated with alcohol use phenotypes in human and mouse models.Addict Biol 15:185-199.
Philibin, S.D., Cameron, A.J., Schlumbohm, J.P., Metten, P., Crabbe, J.C. (2012) Ethanol withdrawal- induced motor impairment in mice. Psychopharmacol 220(2):367-78.
Kendler, K.S., Aggen, S., Prescott, C.A., Crabbe, J.C., Neale, M.C. (2012) Evidence for multiple genetic factors underlying the DSM-IV criteria for alcohol dependence.Mol Psychiat 17:1306-1315.
Crabbe, J.C., Colville, A.M., Kruse, L.C., Cameron, A.J., Spence, S.E., Schlumbohm, J.P., Huang, L.C., Metten, P. (2012) Ethanol tolerance and withdrawal severity in High Drinking in the Dark selectively bred mice. Alcohol Clin Exp Res 36:1152-1161.
Rosenwasser, A.M., Fixaris, M.C., Crabbe, J.C., Brooks, P.C., Ascheid,S. (2012) Escalation of intake under intermittent ethanol access in diverse mouse genotypes. Addict Biol 18:496-507.
Crabbe, J.C., Metten, P., Huang, L.C., Schlumbohm, J.P., Spence, S.E., Barkley-Levenson, A.M., Finn, D.A., Rhodes, J.S., Cameron, A.J. (2012) Ethanol withdrawal-associated drinking and drinking in the dark: Common and discrete genetic contributions. Addict Genet 1:3-11.
Iancu, O., Overbeck, D., Darajkian, P., Metten, P., McWeeney, S., Crabbe, J., Hitzemann, R. (2013) High Drinking in the Dark selected lines and brain gene coexpression networks. Alcohol Clin Exp Res 37:1295-1303.
Bubier J, Jay J, Baker C, Bergeson S., Ohno H., Metten P, Crabbe J, Chesler, E (2014) Identification of a QTL for alcohol preference and withdrawal with integrative functional genomics and precision genetics resources. Genetics 197:1377-1393
Noronha, A.B.C., Cui, C., Harris, R.A., Crabbe, J.C. (Eds) (2014) Neurobiology of Alcohol Dependence, Elsevier/Academic Press, San Diego.
Metten P, Iancu OD, Spence SE, Walter NAR, Oberbeck D, Harrington CA, Colville A, McWeeney S, Phillips TJ, Buck KJ, Crabbe JC, Belknap JK, Hitzemann RJ (2014) Dual trait selection for ethanol consumption and withdrawal: Genetic and transcriptional network effects. Alcoholism: Clin Exp Res. 38:2915-2924.
Barkley-Levenson AM, Crabbe JC (2015) Genotypic and sex differences in anxiety-like behavior and alcohol-induced anxiolysis in High Drinking in the Dark selected mice. Alcohol, epub ahead of print.
Barkley-Levenson AM, Cunningham CL, Smitasin PJ, Crabbe JC (2015) Rewarding and aversive effects of ethanol in High Drinking in the Dark selectively bred mice. Addiction Bio. 20:80-90. [epub ahead of print (2013)].
Barkley-Levenson AM, Crabbe JC (2015) Distinct ethanol drinking microstructure in two replicate lines of mice selected for drinking to intoxication. Genes Brain Behav 14:398-410.
Barkley-Levenson AM, Crabbe JC (2015) Genotypic and sex differences in anxiety-like behavior and alcohol-induced anxiolysis in High Drinking in the Dark select mice. Alcohol 49:29-36.
B.A. (1968) Stanford University
M.A. (1972) University of Colorado
Ph.D. (1973) University of Colorado
Research Fellow, Organon International BV, Oss, the Netherlands
Lecturer, University of California