Differential Gene Expression in the Nucleus Accumbens and Frontal Cortex of Lewis and Fischer 344 Rats Relevant to Drug Addiction

Abstract

Drug addiction results from the interplay between social and biological factors. Among these, genetic variables play a major role. The use of genetically related inbred rat strains that differ in their preference for drugs of abuse is one approach of great importance to explore genetic determinants. Lewis and Fischer 344 rats have been extensively studied and it has been shown that the Lewis strain is especially vulnerable to the addictive properties of several drugs when compared with the Fischer 344 strain. Here, we have used microarrays to analyze gene expression profiles in the frontal cortex and nucleus accumbens of Lewis and Fischer 344 rats. Our results show that only a very limited group of genes were differentially expressed in Lewis rats when compared with the Fischer 344 strain. The genes that were induced in the Lewis strain were related to oxygen transport, neurotransmitter processing and fatty acid metabolism. On the contrary genes that were repressed in Lewis rats were involved in physiological functions such as drug and proton transport, oligodendrocyte survival and lipid catabolism.These data might be useful for the identification of genes which could be potential markers of the vulnerability to the addictive properties of drugs of abuse.

Differential Protein Expression in the Nucleus Accumbens and Amygdala of Lewis and Fischer 344 Rats, and its Relevance in Drug Addiction

“…While 6 proteins were seen to be differentially expressed between the two strains analyzed, none of these coincided with those reported in our earlier microarray study [14].…”

“…The beta subunit of this enzyme is located in the F1 fraction (in the mitochondrial matrix) [18]. We have shown previously that the expression of the ATP synthase F0 subunit 8 gene also differed between LEW and F344 in the NAcc [14]. In addition, the expression of subunit A, another subunit of this enzyme, also differs between rats depending on their ability to extinguish a previously established cocaine-induced CPP [7].…”

“…In order to gain a deeper understanding of the differences between the LEW and F344 strains in terms of gene expression, we originally adopted a transcriptomic approach to analyze the differences in gene expression in the nucleus accumbens and prefrontal cortex in microarrays [14]. We found that only a very limited group of genes were differentially expressed in LEW rats when compared with the Fischer 344 strain.…”

Mechanisms of impulsive choice: II. Time-based interventions to improve self-control

“…One key neurobiological difference in the Lewis strain (compared to control strains) is lower dopamine (and serotonin) functionality in the mesolimbic pathway, particularly the nucleus accumbens (Flores et al 1998; Harris and Nestler 1996; Higuera-Matas et al 2011; Martin et al 1999). The nucleus accumbens has been proposed as a site for integrating delay and magnitude information to form an overall valuation signal (Gregorios-Pippas et al 2009; Kable and Glimcher 2007).…”

Strain Differences in Cannabinoid-Reinforced Lever Press Discrimination

“…For example, through a transcriptome analysis, we identified several genes that are differentially expressed in the nucleus accumbens (NAcc) and prefrontal cortex (PFc) of LEW and F344 rats. The genes induced in the LEW strain were associated with oxygen transport, neurotransmitter processing, and fatty acid metabolism, while those that were repressed were implicated in physiological functions such as drug and proton transport, oligodendrocyte survival, and lipid catabolism [3]. In a more target-specific study, we focused on several parameters of the endogenous opioid system in the encephalon, demonstrating that binding to μ-opioid receptors was weaker in LEW rats than in F344 rats.…”