Peroxisome proliferator-activated receptor (PPAR) agonists are anti-inflammatory compounds that have also been studied for their role in reducing ethanol drinking (Blednov et al., 2014a). PPARs are nuclear hormone receptors that function as ligand-activated transcription factors, and PPAR agonists are approved for treating hyperlipidemia and type 2 diabetes (Chigurupati et al., 2015). The isoforms PPARα, PPARγ, and PPARβ/δ are located throughout most peripheral tissues, as well as in brain regions implicated in AUD (Warden et al., 2016). Table 4 summarizes preclinical studies of PPAR-related treatments on ethanol behaviors. The PPARα agonists fenofibrate and tesaglitazar decrease ethanol consumption and other relevant behaviors in rodents (Barson et al., 2009; Blednov et al., 2014a, 2016a, 2016b; Haile and Kosten, 2017; Karahanian et al., 2014) and also alter the expression of brain genes that were previously shown to regulate drinking behavior (Ferguson et al., 2014). Following fenofibrate treatment, mice treated with ethanol show marked increases in blood acetaldehyde (Karahanian et al., 2014), suggesting that PPARα-dependent effects on ethanol consumption are mediated by increased systemic levels of acetaldehyde. PPARγ activation by pioglitazone reduces ethanol drinking in
