In conclusion, these results demonstrate that changes in alcohol drinking behavior in mice following PPAR agonist administration are accompanied by changes in expression of brain genes, including many of those previously linked with regulation of alcohol consumption. Some of the gene expression changes observed in all three tissues had not been previously implicated in PPAR action. The transcriptional changes in neurons were unexpected and may be important in the behavioral effects of PPAR agonists on ethanol consumption. GABAergic interneurons, neuropeptide systems and dopaminergic signaling pathways may play a role in decreased alcohol drinking since these pathways are important for alcohol action and are associated with the effective PPAR treatments but absent in the non-effective treatment. This is the first microarray analysis of the amygdala and PFC after administration of selective PPAR agonists and will help determine the pharmacogenomic processes by which PPAR agonists decrease alcohol consumption, a critical step if these agents have a future as therapeutics for alcohol dependence.
