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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on June 11, 2008; DOI: 10.1124/jpet.108.137521

0022-3565/08/3263-792-800$20.00
JPET 326:792-800, 2008
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NEUROPHARMACOLOGY

Genomic Insights into Acute Alcohol ToleranceFormula

Wei Hu, Laura Saba, Katherina Kechris, Sanjiv V. Bhave, Paula L. Hoffman, and Boris Tabakoff

Departments of Pharmacology (W.H., L.S., S.V.B., P.L.H., B.T.) and Preventive Medicine and Biometrics (K.K.), University of Colorado School of Medicine, Aurora, Colorado

Alcohol "sensitivity" has been proposed as a predictive factor for development of alcohol dependence (Schuckit et al., 2005). Most measures of alcohol sensitivity in humans and animals include a component that can be ascribed to acute functional tolerance (AFT). AFT is a form of tolerance that develops within a single period of alcohol exposure and has a genetic component. We used microarray technology as well as quantitative trait locus analysis of phenotypic and gene expression data across 30 BXD recombinant inbred strains of mice, 20 inbred strains of mice, and two replicate lines of mice selectively bred for differences in AFT, to identify differentially expressed candidate genes that contribute to predisposition to AFT. Eight candidate genes were identified by our statistical and filtering methods. The location of brain expression of these genes was mapped using the Allen Brain Atlas (http://www.brain-map.org), and the transcript location and molecular pathway analysis indicated that brain structures and biochemical pathways implicated in long-term potentiation and memory might also participate in the generation of acute functional alcohol tolerance.

Received February 4, 2008; accepted June 9, 2008.

Address correspondence to: Dr. Boris Tabakoff, Department of Pharmacology, University of Colorado School of Medicine, Mail Stop 8303, P.O. Box 6511, Aurora, CO 80045-0511. E-mail: boris.tabakoff{at}ucdenver.edu




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