Publication Details

Gene expression changes in the nucleus accumbens of alcohol-preferring rats following chronic ethanol consumption.

Authors:Bell RL, Kimpel MW, McClintick JN, Strother WN, Carr LG, Liang T, Rodd ZA, Mayfield RD, Edenberg HJ, McBride WJ
Title:Gene expression changes in the nucleus accumbens of alcohol-preferring rats following chronic ethanol consumption.
Journal:Pharmacology, biochemistry, and behavior Nov 2009 , Vol 94 , pp. 131-47
Abstract:The objective of this study was to determine the effects of binge-like alcohol drinking on gene expression changes in the nucleus accumbens (ACB) of alcohol-preferring (P) rats. Adult male P rats were given ethanol under multiple scheduled access (MSA; three 1-h dark cycle sessions/day) conditions for 8 weeks. For comparison purposes, a second ethanol drinking group was given continuous/daily alcohol access (CA; 24h/day). A third group was ethanol-naïve (W group). Average ethanol intakes for the CA and MSA groups were approximately 9.5 and 6.5 g/kg/day, respectively. Fifteen hours after the last drinking episode, rats were euthanized, the brains extracted, and the ACB dissected. RNA was extracted and purified for microarray analysis. The only significant differences were between the CA and W groups (p<0.01; Storey false discovery rate=0.15); there were 374 differences in named genes between these 2 groups. There were 20 significant Gene Ontology (GO) categories, which included negative regulation of protein kinase activity, anti-apoptosis, and regulation of G-protein coupled receptor signaling. Ingenuity analysis indicated a network of transcription factors, involving oncogenes (Fos, Jun, Junb had higher expression in the ACB of the CA group), suggesting increased neuronal activity. There were 43 genes located within rat QTLs for alcohol consumption and preference; 4 of these genes (Tgfa, Hspa5, Mtus1 and Creb3l2) are involved in anti-apoptosis and increased transcription, suggesting that they may be contributing to cellular protection and maintaining high alcohol intakes. Overall, these findings suggest that chronic CA drinking results in genomic changes that can be observed during the early acute phase of ethanol withdrawal. Conversely, chronic MSA drinking, with its associated protracted withdrawal periods, results in genomic changes that may be masked by tight regulation of these genes following repeated experiences of ethanol withdrawal.   PUBMED: 19666046
Ontological Annotations:
  • D009714: Nucleus Accumbens (Publication, NCBO Annotator; PubMed MeSH Annotations)
  • GO:0045859: regulation of protein kinase activity (Publication, NCBO Annotator)
  • D016424: Overall (Publication, NCBO Annotator)
  • D020411: Oligonucleotide Array Sequence Analysis (PubMed MeSH Annotations)
  • D000428: Alcohol Drinking (Publication, NCBO Annotator; PubMed MeSH Annotations)
  • D000818: Animals (PubMed MeSH Annotations)
  • GO:0006469: negative regulation of protein kinase activity (Publication, NCBO Annotator)
  • D019204: GTP-Binding Proteins (Publication, NCBO Annotator)
  • D004326: Drinking (Publication, NCBO Annotator)
  • GO:0016301: kinase activity (Publication, NCBO Annotator)
  • GO:0043066: negative regulation of apoptosis (Publication, NCBO Annotator)
  • D001921: Brain (Publication, NCBO Annotator)
  • D005786: Gene Expression Regulation (PubMed MeSH Annotations)
  • D000431: Ethanol (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D030541: Databases, Genetic (PubMed MeSH Annotations)
  • D007091: Image Processing, Computer-Assisted (PubMed MeSH Annotations)
  • D012926: Social Control, Formal (Publication, NCBO Annotator)
  • D000328: Adult (Publication, NCBO Annotator)
  • D009857: Oncogenes (Publication, NCBO Annotator)
  • D011494: Protein Kinases (Publication, NCBO Annotator)
  • GO:0004672: protein kinase activity (Publication, NCBO Annotator)
  • D020133: Reverse Transcriptase Polymerase Chain Reaction (PubMed MeSH Annotations)
  • D005518: Food Preferences (PubMed MeSH Annotations)
  • GO:0005634: nucleus (Publication, NCBO Annotator)
  • D002492: Central Nervous System Depressants (PubMed MeSH Annotations)
  • D012313: RNA (Publication, NCBO Annotator; PubMed MeSH Annotations)
  • D046228: Microarray Analysis (Publication, NCBO Annotator)
  • D001522: Behavior, Animal (PubMed MeSH Annotations)
  • D051381: Rats (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D012646: Self Administration (PubMed MeSH Annotations)
  • GO:0023052: signaling (Publication, NCBO Annotator)
  • GO:0010467: gene expression (Publication, NCBO Annotator)
  • D014157: Transcription Factors (Publication, NCBO Annotator)
  • D010770: Phosphotransferases (Publication, NCBO Annotator)

1 GeneSets from this Publication:


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Expand Tier III Rat 350 Genes GS37147: Gene expression change in the nucleus accumbens, following continuous alcohol consumption in alcohol preferring rats.