This experiment tested whether gemfibrozil, in addition to exerting a physiological effect, alters the brain peptide OX known to stimulate consumption of ethanol, as well as intake of a fat-rich diet (see Introduction). An additional set of rats was examined in the same manner as Experiment 3, except that a between-group design was used. The rats receiving gemfibrozil (50 mg/kg i.g.) compared to vehicle had circulating TG levels that were 35% lower (p < 0.05) (Fig. 4A). They also consumed 52% less ethanol in the first hour of daily access [F(1,1) = 5.99, p < 0.05], thus confirming the results of Experiment 3 (Fig. 4B). To determine the effect of gemfibrozil on OX expression independent of any change in ethanol intake, only rats with similar intakes (n = 5/group) were selected for measurement of peptide mRNA using real-time quantitative PCR. Rats treated with gemfibrozil compared to vehicle exhibited a significant reduction in OX expression in the PFLH (-64%, p < 0.001) (Fig. 4C). Thus, with ethanol intake eliminated as a variable, these results demonstrate that gemfibrozil, while lowering TG, suppresses a peptide known to stimulate ethanol intake, suggesting a mechanism through which this drug may act to reduce ethanol consumption.
