Genomic Insights into Acute Alcohol ToleranceJournal of Pharmacology And Experimental Therapeutics Fast Forward
First published on June 11, 2008
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 which 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, and quantitative trait locus analysis of phenotypic and gene expression data across 30 BXD RI 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 contributing 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 and the transcript location and molecular pathway analysis indicated that brain structures and biochemical pathways implicated in long term potentiation (LTP) and memory may also participate in the generation of acute functional alcohol tolerance.
Request Reprint E-Mail: boris.tabakoff@uchsc.edu
_________________________________________________________________
