Varenicline significantly attenuated both 20% ethanol self-administration and the increases in 20% ethanol operant self-administration caused by chronic nicotine administration. Two-way ANOVA analysis of ethanol consumption revealed a significant effect of pretreatment (0.8mg/kg nicotine or vehicle) [F(1,20=19.9, p<0.001], an effect of varenicline treatment (2mg/kg or vehicle) [F(1,20=16.1, p<0.001] but no interaction between pretreatment × treatment [F(1,20) =1.5, n.s.]. Post hoc analysis revealed an effect of varenicline pretreatment for the saline and the nicotine administered group (Figure 4). Two-way ANOVA of active lever presses revealed a significant effect of nicotine administration (0.8mg/kg or vehicle) [F(1,20=6.0, p<0.05], an effect of varenicline pretreatment (2mg/kg or vehicle) [F(1,20=20.4, p<0.001] but no interaction between nicotine administration × varenicline pretreatment [F(1, 20) =0.44, n.s.]. Post hoc analysis further reveals varenicline significantly decreased active lever pressing for both nicotine and vehicle pretreated groups. There was no overall main effect on the number of inactive lever presses for either nicotine administration or varenicline pretreatment (data not shown).