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

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

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.

Keywords: Drug addiction, gene expression, genetic differences, Fischer 344, Lewis, microarrays, tegmental area (VTA), opioid receptors, morphine, hypothalamic-pituitary-adenal (HPA), proteins