Differences in norepinephrine clearance in cerebellar slices from low-alcohol-sensitive and high-alcohol-sensitive rats.
Differences in norepinephrine clearance in cerebellar slices from low-alcohol-sensitive and high-alcohol-sensitive rats.
复制标题
低度酒精敏感和高度酒精敏感大鼠小脑切片去甲肾上腺素清除率的差异。
DOI：
10.1016/s0741-8329(03)00098-3
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Palmer,MichaelR
中科院分区：
文献类型：
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作者：
Freund,RonaldK;Gerhardt,GregA;Marshall,KristeE;Palmer,MichaelR
培育高酒精敏感（HAS）和低酒精敏感（LAS）大鼠，分别对乙醇的镇静/催眠作用敏感和不敏感。这些大鼠还对局部应用乙醇对体内小脑浦肯野神经元的抑制作用表现出不同的敏感性。我们发现 LAS 动物比 HAS 动物表现出内源性 β-肾上腺素能活性对神经元对 γ-氨基丁酸 (GABA) 和乙醇反应的更大影响。在当前的研究中，我们研究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 HAS 和 LAS 大鼠对 GABA 和乙醇敏感性的 β-肾上腺素能差异影响的可能性。我们将玻璃微量移液器中的去甲肾上腺素局部涂抹到 LAS 和 HAS 大鼠制备的小脑脑切片的各层中，并使用 Nafion 涂层的碳纤维微电极记录去甲肾上腺素清除率的水平。 HAS 大鼠浦肯野细胞层去甲肾上腺素清除速度显着加快约 64%。 LAS 和 HAS 大鼠之间的分子层或颗粒层去甲肾上腺素清除率未发现差异。儿茶酚胺摄取抑制剂诺米芬辛降低了两种大鼠系中去甲肾上腺素的清除率。这些发现支持这样的假设：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导致 LAS 和 HAS 大鼠中浦肯野神经元对乙醇和 GABA 的不同敏感性。
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 β–adrenergic activity on neuronal responses to γ-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 β–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 ∼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.