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

Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202-4887, United States.
Pharmacology Biochemistry and Behavior (Impact Factor: 2.82). 07/2008; 89(4):481-98. DOI: 10.1016/j.pbb.2008.01.023
Source: PubMed

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.

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Available from: Richard L Bell, Sep 27, 2014
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    • "Using a similar approach we compiled findings from several transcriptional profiling studies that have identified differentially expressed genes from alcohol-related studies on D. melanogaster (Morozova et al. 2006, 2007, 2009, 2011; Urizar et al. 2007; Awofala 2010; Kong et al. 2010); from alcohol-related expression studies done on mice (Xu et al. 2001; Daniels and Buck 2002; Tabakoff et al. 2003; Hitzemann et al. 2004; Saito et al. 2004; Treadwell and Singh 2004; Kerns et al. 2005; MacLaren et al. 2006; Mulligan et al. 2006, 2011; Saba et al. 2006; wang et al. 2007; Denmark and Buck 2008; wolstenholme et al. 2011), and transcriptional profiling data on rats (Rimondini et al. 2002; edenberg et al. 2005; worst et al. 2005; Carr et al. 2007; Kimpel et al. 2007; Rodd et al. 2008), and identified human orthologs. In addition, we analyzed six published transcriptional profiling data sets performed on different areas of postmortem human brains and also included candidate genes for alcohol-related phenotypes from the HuGe Navigator database (Lewohl et al. 2000; Mayfield et al. 2002; Sokolov et al. 2003; Iwamoto et al. 2004; Flatscher-Bader et al. 2005; Liu et al. 2006a; Guo et al. 2009). "
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    • " was at least 1 . 4 ( Tables 7 and 8 ) . There was excellent agreement between the microarray and qRT - PCR results . In addition , previous studies from our laboratory reported good agreement , in 30 of 32 genes tested , between the data obtained with microarrays and the results found with qRT - PCR ( Bell et al . , 2009 ; Kimpel et al . , 2007 ; Rodd et al . , 2008 ) . For example , Gsta4 ( Table 7 ) has been previously validated with qRT - PCR in 3 different brain regions of inbred P vs . inbred NP rats ( Kimpel et al . , 2007 ) ."
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    • "Validation studies on key genes, using qRT-PCR, could not be conducted because there was not sufficient sample remaining after the microarray procedure. Previous studies from our laboratory indicated good agreement between the data obtained with microarrays and the results found with qRT-PCR (Bell et al., 2009; Kimpel et al., 2007; Rodd et al., 2008). "
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