did not change ethanol intake at any time point (Figure 1C; Supplemental Figure 1 G,H,I; Supplemental Figure 2 G,H,I; Supplemental Tables 1, 2). A dual PPARα and γ agonist, tesaglitazar (Cronet et al., 2001; Ljung et al., 2002), produced a strong, long-lasting reduction of ethanol intake and preference (Figure 1D; Supplemental Figure 1 J,K; Supplemental Figure 2 J,K; Supplemental Tables 1, 2). However, this drug increased total fluid intake, especially after the first 6 hours (Supplemental Figure 1 L; Supplemental Figure 2 L; Supplemental Tables 1, 2). Finally, the pan agonist bezafibrate (which activates PPARα/γ/δ) (Willson et al., 2000), modestly reduced preference (not intake) after the first 6 hours at the highest dose tested (75 mg/kg) (Figure 1 E; Supplemental Figure 1 M,N,O; Supplemental Figure 2 M,N,O; Supplemental Tables 1, 2). The effects of the PPAR agonists on ethanol intake, preference, and total fluid intake after 24 hours were also calculated (Supplemental Figure 3; Supplemental Table 3). Fenofibrate and tesaglitazar reduced ethanol intake and preference after 24 hours in the two-bottle choice test, as reported for the other time points above. The effectiveness of pioglitazone after 24 hours was weaker compared to its initial effects after 6 hours. Bezafibrate (75
