Based on the evidence for PPARs in regulating ethanol intake in rodents, we assessed the effects of different PPAR agonists on voluntary ethanol consumption in a mouse strain that consumes large amounts of alcohol and examined their effects on gene expression in brain regions important for reducing ethanol consumption. We show that fenofibrate and tesaglitazar decrease ethanol consumption in mice without affecting overall fluid intake, while bezafibrate did not change ethanol consumption. We reasoned that the PPAR treatment-responsive transcript changes in the brain important for reducing ethanol consumption should reflect treatment effectiveness. To the best of our knowledge, this is the first study to demonstrate brain gene expression changes induced by PPAR agonists at doses that decrease alcohol consumption in the amygdala and PFC of mice, two key areas for alcohol dependence.
