John C. Crabbe
Senior Research Career Scientist, VA Medical Center
Professor, Behavioral Neuroscience, OHSU
e-mail: crabbe@ohsu.edu
Major Areas
Pharmacogenetics; tolerance and dependence; gene mapping
Previous Positions
Research Fellow, Organon International BV, Oss, the Netherlands
Lecturer, University of California, Santa Barbara
Education
B.A. (1968) Stanford University
M.A. (1972) University of Colorado
Ph.D. (1973) University of Colorado
Research Interests
I am interested in mouse pharmacogenetic models for sensitivity to and dependence on ethanol. I have selectively bred lines of mice resistant, or susceptible, to the severity of withdrawal from ethanol dependence, and we and other labs are now analyzing the neurobiological mechanisms underlying the large genetic differences in withdrawal achieved in the Withdrawal Seizure-Prone and -Resistant lines. These studies are concentrated on the lines' differential susceptibility to other drugs of abuse, and on other behavioral and biochemical traits indicative of withdrawal from alcohol. We have recently initiated a new project to selectively breed mice for High Drinking in the (circadian) Dark, as part of the Integrative Neuroscience Initiative on Alcoholism consortium.
Other approaches I am using include the study of multiple inbred and recombinant inbred strains of mice. These studies are examining the basis for genetic correlations between susceptibilities to different drugs of abuse. A current interest is the degree to which different behavioral assays tap the same, or different, underlying genetic domains. For example, eleven different measures of motor incoordination we use in the lab do not sort strains in the same way. I am also exploring the role of different environments on patterns of genetic influence on behavior. The strain difference studies also identify strain patterns of sensitivity indicative of the important influence of single genes on drug responses. In collaboration with other investigators in the Portland Alcohol Research Center , we are using statistical techniques for mapping Quantitative Trait Loci (QTLs) in combination with PCR-based molecular biological techniques for establishing genetic markers to identify specific genes of importance. For some candidate genes, we are using available transgenic and knockout mice to explore functional relationships.
Selected Recent Publications
Wahlsten D, Bachmanov A, Finn DA, Crabbe JC . Stability of inbred mouse strain differences in behavior and brain size between laboratories and across decades. Proceedings Nat. Acad. Sci. , in press.
Rhodes JS, Ford MM, Yu CH, Brown LL, Finn DA, Garland Jr T, Crabbe JC (2006) Mouse inbred strain differences in ethanol drinking to intoxication. Genes Brain Behav , in press.
Kliethermes CL, Crabbe JC (2006) Genetic independence of mouse measures of some aspects of novelty seeking. Proceedings Nat. Acad. Sci. 103:5018-5023.
Lovinger DM, Crabbe JC (2005) Laboratory models of alcoholism: Treatment target identification and insight into mechanisms. Nature Neurosci 8:1471-1480.
Metten P, Crabbe JC (2005) Alcohol withdrawal severity in inbred mouse ( Mus musculus ) strains. Behav Neurosci , 119:911-925.
Crabbe JC , Metten P, Cameron AJ, Wahlsten D (2005) An analysis of the genetics of alcohol intoxication in inbred mice. Neurosci Biobehav Rev 28(8):785-802.
Rhodes JS, Best K, Belknap JK, Finn DA, Crabbe JC (2005) Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice. Physiol Behav . 84(1):53-63.
Crabbe JC , Morris RG (2004) Festina lente: Late-night thoughts on high-throughput screening of mouse behavior. Nat Neurosci .7(11):1175-9.
Ponomarev I, Crabbe JC (2004) Characterization of acute functional tolerance to the hypnotic effects of ethanol in mice. Alcohol Clin Exp Res . 28(7):991-7.
Metten P, Best KL, Cameron AJ, Saultz AB , Zuraw JM, Yu C-H, Wahlsten D, Crabbe JC (2004) Observer-rated ataxia: Rating scales for assessment of genetic differences in ethanol-induced intoxication in mice. J Appl Physiol . 97:360-368.
Wahlsten D, Rustay NR, Metten P, Crabbe JC (2003) In search of a better mouse test. TRENDS in Neuroscience 26:132-136.
Rustay NR, Wahlsten D, Crabbe JC (2003) Assessment of genetic susceptibility to ethanol intoxication in mice. Proceedings Nat Acad Sci . 100:2917-2922.
Crabbe JC (2003) Genetic contributions to addiction. Ann Rev Psychol . 53:435-462.