Gene expression in the ventral tegmental area of 5 pairs of rat lines selectively bred for high or low ethanol consumption. Pharmacol. Biochem. Behav. 102: 275-285, 2012.

The objective of this study was to determine if there are common innate differences in gene expression in the ventral tegmental area (VTA) among the selectively bred (a) alcohol-preferring (P) vs. alcohol-non-preferring (NP) rats; (b) high-alcohol-drinking (HAD) vs. low-alcohol-drinking (LAD) rats (both replicates); (c) ALKO alcohol (AA) vs. nonalcohol (ANA) rats; and (d) Sardinian alcohol-preferring (sP) vs. alcohol- nonpreferring (sNP) rats. Microarray analysis indicated that there were between 350 and 1400 unique named genes that were significantly different between the individual line-pairs. Gene Ontology (GO) and Ingenuity Pathways analyses indicated significant categories and networks in common for up to 3 line-pairs, but not for all 5 line-pairs; moreover, there were few genes in common in these categories and networks between any of the individual line-pairs. The overall ANOVA of the combined data for the 5 line-pairs indicated over 1300 significant differences in expression of named genes. However, there were no overlapping genes across all 5 line-pairs. Although there were 8 genes that overlapped in the same direction in 4 of the line-pairs, the differences in the 8 genes were not observed across all the same line-pairs. In conclusion, the findings suggest that there are no common mechanisms within the VTA across these 5 line-pairs of rats that could account for their disparate alcohol drinking characteristics. Instead, different innate mechanisms involving multiple biological systems within the VTA may be contributing to vulnerability to high alcohol drinking behavior in each of the selectively bred line-pairs, and/or other CNS regions are involved that contribute to this behavior.