The cerebellum is widely known as a motor structure because it regulates and controls motor learning, coordination, and balance. However, it is also critical for non-motor functions such as cognitive processing, sensory discrimination, addictive behaviors and mental disorders. The cerebellum has the highest relative abundance of neuronal nitric oxide synthase (nNos) and is sensitive to ethanol. Although it has been demonstrated that the interaction of γ-aminobutyric acid (GABA) and nitric oxide (NO) might play an important role in the regulation of ethanol-induced cerebellar ataxia, the molecular mechanisms through which ethanol regulates nNos function to elicit this behavioral effect have not been studied extensively. Here, we investigated the dose-dependent effects of acute ethanol treatment on motor impairment using the rotarod behavioral paradigm and the alterations of nNos mRNA expression in cerebellum, frontal cortex (FC), hippocampus and striatum. We also examined the link between acute ethanol-induced motor impairment and nNos by pharmacological manipulation of nNos function. We found that acute ethanol induced a dose-dependent elevation of ethanol blood levels which was associated with the impairment of motor coordination performance and decreased expression of cerebellar nNos. In contrast, acute ethanol increased nNos expression in FC but did not to change the expression for this enzyme in striatum and hippocampus. The effects of acute ethanol were attenuated by l-arginine, a precursor for NO and potentiated by 7-nitroindazole (7-NI), a selective inhibitor of nNos. Our data suggests that differential regulation of nNos mRNA expression in cerebellum and frontal cortex might be involved in acute ethanol-induced motor impairment.

中文翻译：

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神经元一氧化氮合酶在急性乙醇引起的运动障碍中的重要作用。

小脑被广泛认为是运动结构，因为它调节和控制运动学习、协调和平衡。然而，它对于认知处理、感觉辨别、成瘾行为和精神障碍等非运动功能也至关重要。小脑的神经元一氧化氮合酶 (nNos) 相对丰度最高，并且对乙醇敏感。尽管已经证明γ-氨基丁酸（GABA）和一氧化氮（NO）的相互作用可能在乙醇诱导的小脑共济失调的调节中发挥重要作用，但乙醇调节nNos功能以引发这种行为的分子机制的影响尚未得到广泛研究。在这里，我们使用转棒行为范式以及小脑、额叶皮层 (FC)、海马和纹状体中 nNos mRNA 表达的变化研究了急性乙醇治疗对运动障碍的剂量依赖性影响。我们还通过对 nNos 功能进行药理学操作，研究了急性乙醇引起的运动障碍与 nNos 之间的联系。我们发现，急性乙醇会导致血液中乙醇水平呈剂量依赖性升高，这与运动协调能力受损和小脑 nNos 表达减少有关。相反，急性乙醇增加了 FC 中 nNos 的表达，但没有改变纹状体和海马中该酶的表达。急性乙醇的作用被 L-精氨酸（NO 的前体）减弱，并被 7-硝基吲唑 (7-NI)（nNos 的选择性抑制剂）增强。我们的数据表明，小脑和额叶皮质中 nNos mRNA 表达的差异调节可能与急性乙醇诱导的运动障碍有关。