Role of neuronal Xlr4 gene expression in cocaine addiction vulnerability: a microarray study in medial prefrontal cortex and Nucleus Accumbens of C57 and DBA mice.

Although several studies have been performed in rodents, non-human primates and humans, the biological basis of vulnerability to develop cocaine addiction remains largely unknown. Exposure to critical early events (as repeated cross fostering (RCF)) has been reported to increase sensitivity to cocaine in adult C57BL/6J female mice. Here we reasoned that by comparing the RCF-induced genes expression alterations in the NAc of adult mice (3 months of age) from two inbred strains (C57 and DBA), we could be able to identify critical genes underlying the adult behavioral phenotype. By a microarray analysis of gene expression (Agilent paltform)in the NAc of adult animals we found, among the several genes modulated, only 2 genes, the X-linked lymphocyte-regulated 4a and 4b (Xlr4a, Xlr4b), that were simultaneously modulated by the early experience in the two strains, but, notably, in opposite direction. All together, these data strongly indicate a critical role for Xlr4, a new yet unexplored candidate gene, in mediating vulnerability to cocaine addiction in mouse. A total of n=31 samples were processed, with 4 samples/group except one group with only 3 samples (C57_mpFC_ctr). The samples are divided into 8 experimental groups, based on the three factors: strain (2 levels=C57 or DBA) X tissue (2 levels=mpFC or Nac) X treatment (2 levels= control or RCF).