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

Richard Bell, Mark W. Kimpel, Jeanette McClintick, Wendy N. Strother, Lucinda G. Carr, Tiebing Liang, Zachary Rodd, R. Dayne Mayfield, Howard Edenberg, William J. McBride

Research output: Contribution to journalArticle

71 Citations (Scopus)

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; 24 h/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.

Original languageEnglish
Pages (from-to)131-147
Number of pages17
JournalPharmacology Biochemistry and Behavior
Volume94
Issue number1
DOIs
StatePublished - Nov 2009

Fingerprint

Nucleus Accumbens
Gene expression
Rats
Ethanol
Alcohols
Gene Expression
Genes
Drinking
Alcohol Drinking
jun Genes
Merozoite Surface Protein 1
Apoptosis
Gene Ontology
Transcription
Microarray Analysis
Microarrays
G-Protein-Coupled Receptors
Protein Kinases
Ontology
Brain

Keywords

  • Alcohol drinking
  • Alcohol-preferring rats
  • Ethanol responsive genes
  • Ethanol withdrawal
  • Gene expression
  • Microarrays
  • Nucleus accumbens
  • Self-administration

ASJC Scopus subject areas

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

Cite this

Gene expression changes in the nucleus accumbens of alcohol-preferring rats following chronic ethanol consumption. / Bell, Richard; Kimpel, Mark W.; McClintick, Jeanette; Strother, Wendy N.; Carr, Lucinda G.; Liang, Tiebing; Rodd, Zachary; Mayfield, R. Dayne; Edenberg, Howard; McBride, William J.

In: Pharmacology Biochemistry and Behavior, Vol. 94, No. 1, 11.2009, p. 131-147.

Research output: Contribution to journalArticle

Bell, Richard ; Kimpel, Mark W. ; McClintick, Jeanette ; Strother, Wendy N. ; Carr, Lucinda G. ; Liang, Tiebing ; Rodd, Zachary ; Mayfield, R. Dayne ; Edenberg, Howard ; McBride, William J. / Gene expression changes in the nucleus accumbens of alcohol-preferring rats following chronic ethanol consumption. In: Pharmacology Biochemistry and Behavior. 2009 ; Vol. 94, No. 1. pp. 131-147.
@article{9729f15ca0b047b7845346aafa027719,
title = "Gene expression changes in the nucleus accumbens of alcohol-preferring rats following chronic ethanol consumption",
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; 24 h/day). A third group was ethanol-na{\"i}ve (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{\circledR} 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.",
keywords = "Alcohol drinking, Alcohol-preferring rats, Ethanol responsive genes, Ethanol withdrawal, Gene expression, Microarrays, Nucleus accumbens, Self-administration",
author = "Richard Bell and Kimpel, {Mark W.} and Jeanette McClintick and Strother, {Wendy N.} and Carr, {Lucinda G.} and Tiebing Liang and Zachary Rodd and Mayfield, {R. Dayne} and Howard Edenberg and McBride, {William J.}",
year = "2009",
month = "11",
doi = "10.1016/j.pbb.2009.07.019",
language = "English",
volume = "94",
pages = "131--147",
journal = "Pharmacology, Biochemistry and Behavior",
issn = "0091-3057",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Gene expression changes in the nucleus accumbens of alcohol-preferring rats following chronic ethanol consumption

AU - Bell, Richard

AU - Kimpel, Mark W.

AU - McClintick, Jeanette

AU - Strother, Wendy N.

AU - Carr, Lucinda G.

AU - Liang, Tiebing

AU - Rodd, Zachary

AU - Mayfield, R. Dayne

AU - Edenberg, Howard

AU - McBride, William J.

PY - 2009/11

Y1 - 2009/11

N2 - 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; 24 h/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.

AB - 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; 24 h/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.

KW - Alcohol drinking

KW - Alcohol-preferring rats

KW - Ethanol responsive genes

KW - Ethanol withdrawal

KW - Gene expression

KW - Microarrays

KW - Nucleus accumbens

KW - Self-administration

UR - http://www.scopus.com/inward/record.url?scp=70349198891&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349198891&partnerID=8YFLogxK

U2 - 10.1016/j.pbb.2009.07.019

DO - 10.1016/j.pbb.2009.07.019

M3 - Article

C2 - 19666046

AN - SCOPUS:70349198891

VL - 94

SP - 131

EP - 147

JO - Pharmacology, Biochemistry and Behavior

JF - Pharmacology, Biochemistry and Behavior

SN - 0091-3057

IS - 1

ER -