Some of the behavioral effects that we observed might be attributed to the systemic effects of PPAR agonists on metabolism. For example, PPAR agonists can affect alcohol and acetaldehyde dehydrogenase mRNAs in the liver (Ferguson et al., 2014), which could increase acetaldehyde and potentially reduce alcohol consumption. However, given the evidence for central action of PPAR agonists on ethanol drinking (Stopponi et. al., 2011), their ability to alter neuronal gene expression in mouse brain following systemic injection (Ferguson et al., 2014), their role in many CNS effects and diseases, and our results showing that the active metabolite of fenofibrate rapidly reaches mouse brain, the effects on ethanol drinking observed in this study are likely mediated via central mechanisms.
