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Differential gene expression in the nucleus accumbens with ethanol self-administration in inbred alcohol-preferring rats.

ABSTRACT: The current study examined the effects of operant ethanol (EtOH) self-administration on gene expression kin the nucleus accumbens (ACB) and amygdala (AMYG) of inbred alcohol-preferring (iP) rats. Rats self-trained on a standard two-lever operant paradigm to administer either water-water, EtOH (15% v/v)-water, or saccharin (SAC; 0.0125% g/v)-water. Animals were killed 24 h after the last operant session, and the ACB and AMYG dissected; RNA was extracted and purified for microarray analysis. For the ACB, there were 513 significant differences at the p<0.01 level in named genes: 55 between SAC and water; 215 between EtOH and water, and 243 between EtOH and SAC. In the case of the AMYG (p<0.01), there were 48 between SAC and water, 23 between EtOH and water, and 63 between EtOH and SAC group. Gene Ontology (GO) analysis indicated that differences in the ACB between the EtOH and SAC groups could be grouped into 15 significant (p<0.05) categories, which included major categories such as synaptic transmission, cell and ion homeostasis, and neurogenesis, whereas differences between the EtOH and water groups had only 4 categories, which also included homeostasis and synaptic transmission. Several genes were in common between the EtOH and both the SAC and water groups in the synaptic transmission (e.g., Cav2, Nrxn3, Gabrb2, Gad1, Homer1) and homeostasis (S100b, Prkca, Ftl1) categories. Overall, the results suggest that changes in gene expression in the ACB of iP rats are associated with the reinforcing effects of EtOH.

SUBMITTER: Rodd ZA

PROVIDER: S-EPMC4516281 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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Differential gene expression in the nucleus accumbens with ethanol self-administration in inbred alcohol-preferring rats.

Rodd Zachary A ZA Kimpel Mark W MW Edenberg Howard J HJ Bell Richard L RL Strother Wendy N WN McClintick Jeanette N JN Carr Lucinda G LG Liang Tiebing T McBride William J WJ

Pharmacology, biochemistry, and behavior 20080226 4

The current study examined the effects of operant ethanol (EtOH) self-administration on gene expression kin the nucleus accumbens (ACB) and amygdala (AMYG) of inbred alcohol-preferring (iP) rats. Rats self-trained on a standard two-lever operant paradigm to administer either water-water, EtOH (15% v/v)-water, or saccharin (SAC; 0.0125% g/v)-water. Animals were killed 24 h after the last operant session, and the ACB and AMYG dissected; RNA was extracted and purified for microarray analysis. For t ...[more]

PMID: 18405950

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Project description:This study investigated changes in gene expression associated with ethanol drinking in adult male P rats under the following conditions for 8 weeks: continuous access (24 hr/day, 7 days/week), multiple scheduled access (three 1-hr sessions during the dark cycle/day, 5 days/week) and ethanol-naive (water). The objective of this study was to investigate changes in gene expression associated with ethanol drinking. Adult male alcohol-preferring (P) rats were given Ethanol in their home-cages under continuous access (CA; 24 hr/day, 7 days/week) or multiple scheduled access (MSA; three 1-hr sessions during the dark cycle/day, 5 days/week) conditions for 8 weeks. A third group was ethanol-naïve (W group). Average ethanol intakes, across the 8 weeks, for the CA and MSA groups were approximately 9.5 and 6.5 g/kg/day, respectively. Fifteen hr after the last ethanol drinking episode, rats were euthanized, the brains rapidly extracted, and the nucleus accumbens (ACB) dissected. RNA was extracted and purified for microarray analysis. The only significant differences, overall, were between the CA and W groups (p < 0.01; Storey false discovery rate = 0.15); there were 374 significant differences in unique named genes between these 2 groups. There were 20 significant Gene Ontology (GO) biological processes categories, which included ‘negative regulation of protein kinase activity’, ‘anti-apoptosis’, and ‘regulation of G-protein-coupled receptor protein signaling pathway’. Ingenuity® analysis indicated a network of transcription factors, involving oncogenes (Fos, Jun, Junb had higher expression levels in the ACB of the CA than W group), suggesting increased neuronal activity in the CA group. There were 13 genes (Hspa5, Stom, Lcn7, Tceb3, Cdc42, Rap1ga1, Ece1, Dhrs3, Plod1, Kif1b, Nmnat1, Srpr, Esam) significantly different between the CA and W groups located within both mouse and rat ethanol QTLs, suggesting that these genes may contribute to ethanol drinking behavior. In conclusion, the robust differences in gene expression found between the CA and W groups, but not observed between the MSA and W groups, may be a result of the higher daily ethanol intakes of the CA group, and/or its initial ethanol withdrawal. Keywords: comparison of gene expression profiles for treated vs. control

Project description:This study investigated changes in gene expression associated with ethanol drinking in adult male P rats under the following conditions for 8 weeks: continuous access (24 hr/day, 7 days/week), multiple scheduled access (three 1-hr sessions during the dark cycle/day, 5 days/week) and ethanol-naive (water). The objective of this study was to investigate changes in gene expression associated with ethanol drinking. Adult male alcohol-preferring (P) rats were given Ethanol in their home-cages under continuous access (CA; 24 hr/day, 7 days/week) or multiple scheduled access (MSA; three 1-hr sessions during the dark cycle/day, 5 days/week) conditions for 8 weeks. A third group was ethanol-naÃÂ¯ve (W group). Average ethanol intakes, across the 8 weeks, for the CA and MSA groups were approximately 9.5 and 6.5 g/kg/day, respectively. Fifteen hr after the last ethanol drinking episode, rats were euthanized, the brains rapidly extracted, and the nucleus accumbens (ACB) dissected. RNA was extracted and purified for microarray analysis. The only significant differences, overall, were between the CA and W groups (p < 0.01; Storey false discovery rate = 0.15); there were 374 significant differences in unique named genes between these 2 groups. There were 20 significant Gene Ontology (GO) biological processes categories, which included Ã¢ÂÂnegative regulation of protein kinase activityÃ¢ÂÂ, Ã¢ÂÂanti-apoptosisÃ¢ÂÂ, and Ã¢ÂÂregulation of G-protein-coupled receptor protein signaling pathwayÃ¢ÂÂ. IngenuityÃÂ® analysis indicated a network of transcription factors, involving oncogenes (Fos, Jun, Junb had higher expression levels in the ACB of the CA than W group), suggesting increased neuronal activity in the CA group. There were 13 genes (Hspa5, Stom, Lcn7, Tceb3, Cdc42, Rap1ga1, Ece1, Dhrs3, Plod1, Kif1b, Nmnat1, Srpr, Esam) significantly different between the CA and W groups located within both mouse and rat ethanol QTLs, suggesting that these genes may contribute to ethanol drinking behavior. In conclusion, the robust differences in gene expression found between the CA and W groups, but not observed between the MSA and W groups, may be a result of the higher daily ethanol intakes of the CA group, and/or its initial ethanol withdrawal. Experiment Overall Design: 10 samples each of control, continuous ethanol and limited access ethanol

Dataset Information

Differential gene expression in the nucleus accumbens with ethanol self-administration in inbred alcohol-preferring rats.

Publications

Differential gene expression in the nucleus accumbens with ethanol self-administration in inbred alcohol-preferring rats.

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