G protein–coupled receptors (GPCRs) constitute the largest class of cell surface signaling receptors and regulate major neurobiological processes. Accordingly, GPCRs represent primary targets for the treatment of brain disorders. Several human genetic polymorphisms affecting GPCRs have been associated to different components of alcohol use disorder (AUD). Moreover, GPCRs have been reported to contribute to several features of alcohol-related behaviors in animal models. Besides traditional pharmacological tools, genetic-based approaches mostly aimed at deleting GPCR genes provided substantial information on how key GPCRs drive alcohol-related behaviors. In this review, we summarize the alcohol phenotypes that ensue from genetic manipulation, in particular gene deletion, of key GPCRs in rodents. We focused on GPCRs that belong to fundamental neuronal systems that have been shown as potential targets for the development of AUD treatment. Data are reviewed with particular emphasis on alcohol reward, seeking, and consumption which are behaviors that capture essential aspects of AUD. Literature survey indicates that in most cases, there is still a gap in defining the intracellular transducers and the functional crosstalk of GPCRs as well as the neuronal populations in which their signaling regulates alcohol actions. Further, the implication of only a few orphan GPCRs has been so far investigated in animal models. Combining advanced pharmacological technologies with more specific genetically modified animals and behavioral preclinical models is likely necessary to deepen our understanding in how GPCR signaling contributes to AUD and for drug discovery.

中文翻译：

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GPCR 和转基因小鼠的酒精相关行为。

G 蛋白偶联受体 (GPCRs) 构成最大的一类细胞表面信号受体并调节主要的神经生物学过程。因此，GPCR 代表了治疗脑部疾病的主要目标。影响 GPCR 的几种人类遗传多态性与酒精使用障碍 (AUD) 的不同成分有关。此外，据报道，GPCR 有助于动物模型中酒精相关行为的几个特征。除了传统的药理学工具外，主要旨在删除 GPCR 基因的基于遗传的方法提供了有关关键 GPCR 如何驱动酒精相关行为的大量信息。在这篇综述中，我们总结了啮齿动物关键 GPCR 的基因操作，特别是基因缺失导致的酒精表型。我们专注于属于基本神经元系统的 GPCR，这些系统已被证明是开发 AUD 治疗的潜在目标。审查数据时特别强调了酒精奖励、寻求和消费，这些行为捕捉了澳元的基本方面。文献调查表明，在大多数情况下，在定义细胞内传感器和 GPCR 的功能串扰以及它们的信号调节酒精作用的神经元群体方面仍然存在差距。此外，迄今为止，仅在动物模型中研究了少数孤儿 GPCR 的含义。