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

A Higuera-Matas,S M Coria,C Garcia-Lecumberri,E Ambrosio,M Miguens,G L Montoya

doi:10.2174/157015911795017290

A Higuera-Matas, S M Coria + Show 4 more

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https://doi.org/10.2174/157015911795017290

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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.

Highlights

Drug addiction arises from the interplay between social and biological factors
For the sake of clarity, we have organized the data according to induction/inhibition and anatomical localization criteria (See Tables 1-6)
The number of genes that were significantly induced in the frontal cortex (FC) and not in the nucleus accumbens (NAcc) was higher in the LEW strain compared with the Fischer 344 (F344) strain

Summary

Introduction

Genetic variables are thought to play a major role [1, 2] This fact has been corroborated in animal studies, especially in those involving Lewis (LEW) and Fischer 344 (F344) rats. These two rat strains show differential responses to both drugs of abuse and stressors [3]. There are differences in the levels of μ opioid receptors in several brain regions between both strains and these proteins are differentially modulated after morphine self-administration and during the extinction of this behavior [8]. It has been shown that there are higher levels of dopamine in the NAcc-Core of LEW rats after acute administration of several drugs of abuse [15]

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