PDF(Pubmed)
Abstract：
Alcohol tolerance is a neuroadaptive response that leads to a reduction in the effects of alcohol caused by previous exposure. Tolerance plays a critical role in the development of alcohol use disorder (AUD) because it leads to the escalation of drinking and dependence. Understanding the molecular mechanisms underlying alcohol tolerance is therefore important for the development of effective therapeutics and for understanding addiction in general. This review explores the molecular basis of alcohol tolerance in invertebrate models, Drosophila and C. elegans, focusing on synaptic transmission. Both organisms exhibit biphasic responses to ethanol and develop tolerance similar to that of mammals. Furthermore, the availability of several genetic tools makes them a great candidate to study the molecular basis of ethanol response. Studies in invertebrate models show that tolerance involves conserved changes in the neurotransmitter systems, ion channels, and synaptic proteins. These neuroadaptive changes lead to a change in neuronal excitability, most likely to compensate for the enhanced inhibition by ethanol.
摘要：
酒精耐受性是一种神经适应性反应，可减少先前暴露引起的酒精影响。耐受性在酒精使用障碍（AUD）的发展中起着至关重要的作用，因为它导致饮酒和依赖的升级。因此，了解酒精耐受性的分子机制对于开发有效的治疗方法和总体上了解成瘾非常重要。这篇综述探讨了无脊椎动物模型中酒精耐受性的分子基础，果蝇和秀丽隐杆线虫,专注于突触传递。两种生物都表现出对乙醇的双相反应，并产生与哺乳动物相似的耐受性。此外，几种遗传工具的可用性使它们成为研究乙醇反应分子基础的绝佳候选者。无脊椎动物模型的研究表明，耐受性涉及神经递质系统的保守变化，离子通道,和突触蛋白。这些神经适应性变化导致神经元兴奋性的变化，最有可能补偿乙醇增强的抑制作用。
