Gene expression in the ventral tegmental area of 5 pairs of rat lines selectively bred for high or low ethanol consumption

William J. McBride, Mark W. Kimpel, Jeanette N. McClintick, Zheng Ming Ding, Petri Hyytia, Giancarlo Colombo, Howard J. Edenberg, Lawrence Lumeng, Richard L. Bell

Research output: Contribution to journalArticle

35 Scopus citations


The objective of this study was to determine if there are common innate differences in gene expression or gene pathways in the ventral tegmental area (VTA) among 5 different pairs of rat lines selectively bred for high (HEC) or low (LEC) ethanol consumption: (a) alcohol-preferring (P) vs. alcohol-non-preferring (NP) rats; (b) high-alcohol-drinking (HAD) vs. low-alcohol-drinking (LAD) rats (replicate line pairs 1 and 2); (c) ALKO alcohol (AA) vs. nonalcohol (ANA) rats; and (d) Sardinian alcohol-preferring (sP) vs. alcohol-nonpreferring (sNP) rats. Microarray analysis revealed between 370 and 1340 unique named genes that significantly differed in expression between the individual line-pairs. Analysis using Gene Ontology (GO) and Ingenuity Pathways information 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. ANOVA of the combined data for the 5 line-pairs indicated 1295 significant (p < 0.01) differences in expression of named genes. Although no individual named gene was significant across all 5 line-pairs, there were 22 genes that overlapped in the same direction in 3 or 4 of the line-pairs. Overall, the findings suggest that (a) some biological categories or networks may be in common for subsets of line-pairs; and (b) regulation of different genes and/or combinations of multiple biological systems (e.g., transcription, synaptic function, intracellular signaling and protection against oxidative stress) within the VTA (possibly involving dopamine and glutamate) may be contributing to the disparate alcohol drinking behaviors of these line-pairs.

Original languageEnglish (US)
Pages (from-to)275-285
Number of pages11
JournalPharmacology Biochemistry and Behavior
Issue number2
StatePublished - Aug 1 2012


  • Alcohol-preferring
  • ALKO alcohol
  • Gene expression
  • High-alcohol-drinking
  • Sardinian alcohol-preferring
  • Selectively-bred rat lines
  • Ventral tegmental area

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology
  • Toxicology
  • Behavioral Neuroscience
  • Biological Psychiatry

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