Savelieva Katerina V, Caudle W Michael, Miller Gary W
Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas, Waggoner Center for Alcohol and Addiction Research, Austin, Texas 78712, USA.
Alcohol. 2006 Oct;40(2):87-94. doi: 10.1016/j.alcohol.2006.09.030.
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.
本研究的目的是利用囊泡单胺转运体2（VMAT2）杂合子敲除小鼠[VMAT2(+/-)]，研究VMAT2基因敲低对自愿乙醇摄入和条件性位置偏爱（CPP）的影响。在双瓶选择程序中评估乙醇偏爱和摄入量，并使用CPP范式确定乙醇的奖赏特性。在双瓶选择实验中，与野生型同窝小鼠相比，VMAT2(+/-)雄性小鼠在所有测试浓度下对乙醇的偏爱和摄入量均降低。虽然雌性小鼠比雄性小鼠摄入更多乙醇，但野生型和VMAT2(+/-)之间没有差异。在CPP实验中，野生型小鼠对与乙醇配对的环境表现出位置偏爱，而雄性和雌性VMAT2(+/-)小鼠均未形成位置偏爱。野生型和VMAT2(+/-)小鼠在血液乙醇代谢和对乙醇抑制作用的敏感性方面没有差异。这些数据表明，VMAT2表达降低会减少雄性小鼠的乙醇摄入量，并消除两性杂合子小鼠的位置偏爱，提示VMAT2表达改变可能与乙醇的奖赏特性有关。
