Increased sensitivity to the aversive effects of ethanol in PKCepsilon null mice revealed by place conditioning.

Determining the intracellular signaling pathways that mediate the rewarding effects of ethanol may help identify drug targets to curb excessive alcohol consumption. Mice lacking the epsilon isoform of protein kinase C (PKCepsilon) voluntarily consumed less ethanol than wild-type mice in two-bottle choice and operant self-administration assays. Decreased consumption may reflect either increased or decreased sensitivity to the rewarding effects of ethanol. Alternatively, decreased voluntary consumption may reflect a change in sensitivity to the aversive effects of ethanol. The authors used place conditioning to determine that PKCepsilon null mice have an increased sensitivity to the aversive effects of ethanol but a decreased sensitivity to the rewarding effects of ethanol. Together these data suggest that PKCepsilon null mice voluntarily consume less ethanol because they derive less reward and are more sensitive to the aversive effects of ethanol.