Enhanced ethanol-, but not cocaine-induced, conditioned place preference in Apoe^-/- mice

Apolipoprotein (apo) E is a glycoprotein that is most commonly associated with cardiovascular and Alzheimer's disease risk. Recent data showing that apoE mRNA expression is reduced in the frontal cortex of alcoholics raise the possibility that apoE may also be related to the rewarding properties of ethanol. In this study, we examined whether Apoe deletion affects the rewarding properties of ethanol in mice. Male and female wild-type (WT; C57BL/6J) and apoE knockout (Apoe^-/-; C57BL/6J-Apoe^tm1Unc) mice underwent an unbiased place conditioning procedure with ethanol (2 g/kg) or cocaine (5 mg/kg). Female mice were also tested for ethanol intake in a two-bottle choice procedure. Apoe^-/- mice showed greater ethanol-induced conditioned place preference (CPP). In contrast, cocaine-induced CPP and ethanol intake were similar between the genotypes. These findings suggest that apoE normally reduces the conditioned rewarding properties of ethanol but not of cocaine. While the exact mechanisms underlying these effects of apoE are unknown, these data support a possible role for apoE in modulating the conditioned rewarding properties of ethanol.