Graduate Studies Faculty
John C. Crabbe, Ph.D.
Neuroscience Graduate Program
Research Interests:mouse behavior genetics; alcohol and drug abuse; genetic animal models; drug dependence; drug tolerance » PubMed Listing
Preceptor RotationsAcademic Term Available Winter 2014 Yes Spring 2014 Yes Fall 2014 Yes
Faculty MentorshipDr. Crabbe might be available as a mentor for 2013-2014. Dr. Crabbe might be available as a mentor for 2014-2015.
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.
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 Pharmacol Sci 29:537-543.
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.
Barkley-Levenson, A.M.,Crabbe, J.C. (2012) Ethanol drinking microstructure of a High Drinking in the Dark selected line. Alcohol Clin Exp Res 36:1330-1339.
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.
Tanchuck, M., He, I., Kaufman, K., Snelling, C., Crabbe, J., Mark, G., Finn, D. (2012) Local changes in neurosteroid levels in the substantia nigra reticulata and the ventral tegmental area alter chronic ethanol withdrawal severity in male Withdrawal Seizure-Prone mice. Alcohol Clin Exp Res 37:784-793.
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, in press.
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, in press.
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