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首页> 外文期刊>Alcohol >Differences in norepinephrine clearance in cerebellar slices from low-alcohol-sensitive and high-alcohol-sensitive rats.
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Differences in norepinephrine clearance in cerebellar slices from low-alcohol-sensitive and high-alcohol-sensitive rats.

机译:低酒精敏感性和高酒精敏感性大鼠小脑切片中去甲肾上腺素清除率的差异。

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High-alcohol-sensitive (HAS) and low-alcohol-sensitive (LAS) rats were bred for sensitivity and insensitivity, respectively, to the sedative/hypnotic effects of ethanol. These rats also display differential sensitivity to the depressant effects of locally applied ethanol on cerebellar Purkinje neurons in vivo. We have found that LAS animals exhibit a greater influence of endogenous beta-adrenergic activity on neuronal responses to gamma-aminobutyric acid (GABA) and ethanol than do HAS animals. In the current study, we investigated the possibility that the regulation of synaptic norepinephrine levels by norepinephrine transporters could contribute to a differential beta-adrenergic influence on GABA and ethanol sensitivity between HAS and LAS rats. We locally applied norepinephrine from a glass micropipette into the various layers of cerebellar brain slices prepared from LAS and HAS rats, and recorded the levels of norepinephrine clearance by using Nafion-coated carbon-fiber microelectrodes. Norepinephrine clearance was significantly faster by approximately 64% in the Purkinje cell layer of HAS rats. No differences in norepinephrine clearance were found in the molecular or the granule layer between LAS and HAS rats. The catecholamine uptake inhibitor nomifensine reduced norepinephrine clearance in both rat lines. These findings support the hypothesis that regulation of synaptic norepinephrine levels by norepinephrine transporter activity in the Purkinje cell layer may contribute to the differential sensitivity of Purkinje neurons to ethanol and GABA in LAS and HAS rats.
机译:饲养高酒精敏感性(HAS)和低酒精敏感性(LAS)大鼠分别对乙醇的镇静/催眠作用敏感和不敏感。这些大鼠还表现出对体内应用乙醇对小脑浦肯野神经元的抑制作用的不同敏感性。我们已经发现,与HAS动物相比,LAS动物表现出更大的内源性β-肾上腺素能活动对神经元对γ-氨基丁酸(GABA)和乙醇的反应。在当前的研究中,我们调查了去甲肾上腺素转运蛋白对突触去甲肾上腺素水平的调节可能有助于在HAS和LAS大鼠之间对GABA和乙醇敏感性产生不同的β-肾上腺素影响。我们从玻璃微量移液器中将去甲肾上腺素局部应用到由LAS和HAS大鼠制备的小脑大脑切片的各个层中,并通过使用Nafion涂层碳纤维微电极记录去甲肾上腺素清除水平。在HAS大鼠的Purkinje细胞层中,去甲肾上腺素的清除明显加快了约64%。在LAS和HAS大鼠之间的分子或颗粒层中,去甲肾上腺素清除率没有差异。儿茶酚胺摄取抑制剂诺米芬降低了两种大鼠品系中去甲肾上腺素的清除率。这些发现支持以下假设:浦肯野细胞层中去甲肾上腺素转运蛋白活性对突触去甲肾上腺素水平的调节可能有助于浦肯野神经元对LAS和HAS大鼠中乙醇和GABA的敏感性差异。

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