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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Age-dependent changes in the susceptibility to thiopental anesthesia in mice: Analysis of the relationship to the functional expression of GABA transporter
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Age-dependent changes in the susceptibility to thiopental anesthesia in mice: Analysis of the relationship to the functional expression of GABA transporter

机译：小鼠对硫喷妥钠麻醉的敏感性的年龄依赖性变化：与GABA转运蛋白功能表达的关系分析

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The potency of anesthetics changes during development, probably due not only to pharmacokinetic factors such as differential distribution and/or metabolism, but also to pharmacodynamic factors such as changes to the GABAergic system in the brain. To explore the latter mechanism, we focused on the GABA transporter (GAT), the uptake system for GABA, which participates in the synaptic clearance of GABA. Thiopental-induced anesthesia, as assessed by the onset and duration of loss of the righting reflex, was more pronounced in 3-week-old mice than in 7-week-old mice. Both NO-711 and SKF89976A, selective GAT-1 inhibitors, significantly enhanced the anesthesia in the 7-week-old but not in the 3-week-old mice. In synaptosomes prepared from the cerebral cortex, the kinetics of GABA transport was similar between the two age groups, as assessed by [ 3H]GABA uptake assay. In addition, expression of GAT mRNA was similar between the two age groups, as assessed by quantitative RT-PCR. Thiopental reduced [ 3H]GABA uptake only at high concentrations in a similar manner at both ages. Conversely, the ability of SKF89976A to inhibit [ 3H]GABA uptake was greater in the 7-week-old mice than in the 3-week-old mice. Based on these results, GAT seems unlikely to contribute to the greater susceptibility to thiopental anesthesia in 3-week-old mice, while the increased ability of GABA uptake inhibitors to enhance thiopental-induced anesthesia in 7-week-old mice is at least partly due to higher sensitivity of GAT to the inhibitors.
机译：麻醉药的效力在发育过程中发生变化，这可能不仅是由于药代动力学因素（例如差异分布和/或新陈代谢），而且还由于药效动力学因素（例如脑中GABA能系统的变化）所致。为了探索后者的机制，我们集中于GABA转运蛋白（GAT），即GABA的摄取系统，该系统参与GABA的突触清除。通过扶正反射丧失的开始和持续时间评估，硫喷妥钠诱导的麻醉在3周龄小鼠中比在7周龄小鼠中更为明显。选择性的GAT-1抑制剂NO-711和SKF89976A都显着增强了7周龄小鼠的麻醉效果，但对3周龄小鼠却没有增强作用。在通过大脑皮层制备的突触小体中，两个年龄段之间的GABA转运动力学相似，这是通过[3H] GABA摄取测定法评估的。此外，通过定量RT-PCR评估，两个年龄组之间的GAT mRNA表达相似。在两个年龄段，硫喷妥钠仅以相似的方式降低了[3 H] GABA的吸收。相反，在7周龄的小鼠中，SKF89976A抑制[3H] GABA摄取的能力比在3周龄的小鼠中更大。根据这些结果，GAT似乎不太可能导致3周龄小鼠对硫喷妥钠的敏感性更高，而GABA摄取抑制剂增强7周龄小鼠的硫喷妥钠诱导的麻醉的能力增强至少部分是因为由于GAT对抑制剂的敏感性更高。

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