Effects of LY466195, a selective kainate receptor antagonist, on ethanol preference and drinking in rats

There is evidence that variation in the gene encoding a kainate receptor subunit contributes to alcohol dependence risk. Further, there is suggestive evidence that alcohol consumption is mediated, in part, by kainate receptors. In this study, we used a novel kainate receptor antagonist, LY466195, to examine the potential role of kainate receptors in alcohol drinking behavior using a rodent model of voluntary ethanol consumption. Male Sprague Dawley and Long Evans rats were given access to 20% ethanol using the intermittent two-bottle choice paradigm. Following 6 weeks of ethanol consumption, rats were pretreated with an acute dose of LY466195 (0, 4.0 and 10.0mg/kg, i.p.) prior to a two-bottle choice test session. Acute administration of LY466195 did not significantly affect ethanol-drinking behavior in Sprague Dawley rats. In contrast, Long Evans rats pretreated with 10.0mg/kg LY466195 showed a significant reduction in alcohol preference compared to vehicle-treated controls. Decreased alcohol preference in the Long Evans rats was associated with increased water intake and no change in the amount of ethanol consumed. Taken together, these results suggest that systemic administration of a selective kainate receptor antagonist reduces ethanol preference in rats, an effect that could be due to non-specific effects on overall drinking behavior.