Candidate genes for alcohol preference identified by expression profiling in alcohol-preferring and -nonpreferring reciprocal congenic rats

Abstract

Selectively bred alcohol-preferring (P) and alcohol-nonpreferring (NP) rats differ greatly in alcohol preference, in part due to a highly significant quantitative trait locus (QTL) on chromosome 4. Alcohol consumption scores of reciprocal chromosome 4 congenic strains NP.P and P.NP correlated with the introgressed interval. The goal of this study was to identify candidate genes that may influence alcohol consumption by comparing gene expression in five brain regions of alcohol-naïve inbred alcohol-preferring and P.NP congenic rats: amygdala, nucleus accumbens, hippocampus, caudate putamen, and frontal cortex. Results

Within the QTL region, 104 cis-regulated probe sets were differentially expressed in more than one region, and an additional 53 were differentially expressed in a single region. Fewer trans-regulated probe sets were detected, and most differed in only one region. Analysis of the average expression values across the 5 brain regions yielded 141 differentially expressed cis-regulated probe sets and 206 trans-regulated probe sets. Comparing the present results from inbred alcohol-preferring vs. congenic P.NP rats to earlier results from the reciprocal congenic NP.P vs. inbred alcohol-nonpreferring rats demonstrated that 74 cis-regulated probe sets were differentially expressed in the same direction and with a consistent magnitude of difference in at least one brain region. Conclusions

Cis-regulated candidate genes for alcohol consumption that lie within the chromosome 4 QTL were identified and confirmed by consistent results in two independent experiments with reciprocal congenic rats. These genes are strong candidates for affecting alcohol preference in the inbred alcohol-preferring and inbred alcohol-nonpreferring rats.