Altered ethanol-associated behaviors in vesicular monoamine transporter heterozygote knockout mice

The purpose of this study was to examine the effects of the genetic reduction of vesicular monoamine transporter 2 (VMAT2) on voluntary ethanol consumption and conditioned place preference (CPP) using VMAT2 heterozygote knockout mice [VMAT2(+/-)]. Ethanol preference and consumption were assessed in a two-bottle choice procedure, and rewarding properties of ethanol were determined using a CPP paradigm. In the two-bottle choice VMAT2(+/-) male mice exhibited a decreased preference for and consumption of ethanol at all concentrations tested, as compared to their wild-type littermates. While female mice consumed more ethanol than male mice, there was no difference between the wild type and VMAT2(+/-). In the CPP experiment, wild-type mice exhibited place preference for the ethanol-paired environment while neither male or female VMAT2(+/-) mice developed place preference. Wild type and VMAT2(+/-) mice did not differ in blood ethanol metabolism and sensitivity to the depressant effects of ethanol. These data demonstrate that a reduction of VMAT2 expression reduces ethanol consumption in male mice and eliminates place preference in heterozygote mice of both sexes and suggests that altered VMAT2 expression may contribute to the rewarding properties of ethanol.