Alcoholism and alcohol use disorders are chronically relapsing conditions which is a major problem in treating alcohol addiction. In a previous study we showed that the dopamine transporter (DAT) is implicated in voluntary intake and preference. However, its role in modulating ethanol-associated contextual memory remains largely unknown. In this study we have investigated the role of DAT in ethanol-induced conditioned place preference (EtOH-CPP) acquisition and reinstatement in adult male C57BL/6 mice. For this purpose, we used both loss- and gain-of-function approaches to test the effects of central DAT manipulation on EtOH-CPP. We developed a lentiviral-mediated gene transfer approach to examine whether DAT knockdown (shDAT) or overexpression in the nucleus accumbens (Nacc) is enough to impair EtOH-CPP acquisition and reinstatement. In the first experiment, results showed that DAT knockdown blocked, whereas DAT overexpression, exacerbated the acquisition of EtOH-CPP. In the second experiment and after the EtOH-CPP expression, the mice were subjected to a 14-day extinction trials before drug-induced EtOH-CPP reinstatement was induced by a priming injection of 1 g/kg EtOH. Results indicated that reinstatement of EtOH-CPP was considerably decreased after accumbal shDAT injection. However, DAT overexpression significantly increased EtOH-CPP reinstatement. Finally, and following DAT mRNA quantification using RT-PCR, Pearson's correlation showed a strong positive relationship between accumbal DAT mRNA and EtOH-CPP acquisition and reinstatement. These results suggest that DAT expression in the Nacc is involved in the acquisition and retrieval of EtOH contextual memory and that blockade of this transporter can decrease the rewarding properties of EtOH.

中文翻译：

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伏隔核内多巴胺转运蛋白基因的表达在小鼠乙醇获取行为的获取和恢复中起重要作用。

酒精中毒和酒精使用障碍是长期复发的疾病，这是治疗酒精成瘾的主要问题。在先前的研究中，我们表明多巴胺转运蛋白（DAT）与自愿摄入量和偏好有关。但是，其在调节与乙醇相关的背景记忆中的作用仍然未知。在这项研究中，我们研究了DAT在成年雄性C57BL / 6小鼠中乙醇诱导的条件性位置偏爱（EtOH-CPP）采集和恢复中的作用。为此，我们同时使用了功能丧失和功能获得两种方法来测试中央DAT操纵对EtOH-CPP的影响。我们开发了一种慢病毒介导的基因转移方法，以检查DAT敲低（shDAT）或伏隔核（Nacc）的过表达是否足以损害EtOH-CPP的获得和恢复。在第一个实验中，结果显示DAT敲低被阻止，而DAT的过表达加剧了EtOH-CPP的获得。在第二个实验中，在EtOH-CPP表达后，对小鼠进行了14天的灭绝试验，然后通过初次注射1 g / kg EtOH诱导药物诱导的EtOH-CPP恢复。结果表明，正确注射shDAT后，EtOH-CPP的恢复显着降低。但是，DAT过表达显着增加了EtOH-CPP的恢复。最后，在使用RT-PCR对DAT mRNA进行定量后，Pearson的相关性表明，累积DAT mRNA与EtOH-CPP的获取和恢复之间存在很强的正相关。