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 in 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 waterwater, EtOH (15% v/v)-water, or saccharin (SAC; 0.0125% g/v)-water. Animals were killed 24 hr 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, Nrxn, Gabrb2, Gad1, Homer1) and homeostasis Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript (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.

Gene expression changes in serotonin, GABA-A receptors, neuropeptides and ion channels in the dorsal raphe nucleus of adolescent alcohol-preferring (P) rats following binge-like alcohol drinking

“…These previous studies predominantly used the hippocampus, ventral tegmental area, accumbens, amygdala or sub-regions of these areas. (Bell et al, 2009; Kimpel et al, 2007; McBride et al, 2013a; McBride et al, 2012; McBride et al, 2013b; McBride et al, 2010; Rodd et al, 2008). None examined the DRN.…”

Identification of a QTL in Mus musculus for Alcohol Preference, Withdrawal, and Ap3m2 Expression Using Integrative Functional Genomics and Precision Genetics

“…It is in the intersection of QTL for these behaviors, is found to be differentially expressed in numerous studies of alcohol preference (Mulligan et al 2006;Rodd et al 2008;Ponomarev et al 2012), and has been shown to be related to seizure in gene perturbation studies (Nakatsu et al 2004;Misawa et al 2008). The absence of functional polymorphisms in Ap3m2, the discovery of a cis eQTL at Ap3m2 in the BXD population, and the finding of differential expression of Ap3m2 in iWSP-2 and iWSR-1 mice suggest that a common polymorphism affecting Ap3m2 expression is responsible for the heightened alcohol preference and withdrawal.…”

What Aspects of Human Alcohol Use Disorders Can Be Modeled Using Selectively Bred Rat Lines?

“…Some of the neurochemical systems found to be involved in mediating alcohol abuse and alcoholism include the serotonergic, dopaminergic, opioidergic, GABAergic, cholinergic, and glutamatergic systems (for review see Engleman et al, 2006;Froehlich, 1993;Li et al, 1988Li et al, , 1998Liu et al, 2007;Rodd et al, 2007Rodd et al, , 2008. There are a number of neurochemical characteristics within these systems that are associated with, and may be causally related to, differences in alcohol intake (Badia-Elder et al, 1999;Froehlich et al, 1998;Froehlich and Li, 1989, 1994Wand, 1996, 1997;Gong et al, 1997;Kimpel et al, 2003Kimpel et al, , 2007.…”