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钾通道阻滞剂蜂毒明肽和4-氨基吡啶对东莨菪碱诱导的大鼠位置延迟匹配任务缺陷的影响:与胆碱酯酶抑制剂E2020的比较

Effects of the potassium channel blockers, apamin and 4-aminopyridine, on scopolamine-induced deficits in the delayed matching to position task in rats: a comparison with the cholinesterase inhibitor E2020.

作者信息

Poorheidari G, Stanhope K J, Pratt J A

机构信息

Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, UK.

出版信息

Psychopharmacology (Berl). 1998 Feb;135(3):242-55. doi: 10.1007/s002130050506.

DOI:10.1007/s002130050506
PMID:9498727
Abstract

The effects of the muscarinic antagonists, scopolamine HBr and MeBr, a cholinesterase inhibitor, E2020, and K+ channel blockers, 4-aminopyridine (4-AP) and apamin, on the performance of rats in a delayed matching to position (DMTP) task were examined. The percentage of correct choices (choice accuracy), number of trials completed and intertrial intervals were measured. Discriminability and response bias were also calculated, using signal detection analysis. Scopolamine HBr (0.1 mg/kg), but not scopolamine MeBr (0.1 mg/kg), significantly and consistently reduced the choice accuracy and discriminability, but neither affected the other measurements. E2020 (0.03-1.0 mg/kg) had no effect on the baseline performance in the DMTP task, but at 1.0 mg/kg, it significantly attenuated the deficits in choice accuracy induced by scopolamine. 4-AP (0.001-0.1 mg/kg) had no effect on either baseline performance or deficits induced by scopolamine. Apamin (0.1-0.4 mg/kg) had no effect on choice accuracy and discriminability. Apamin also failed to attenuate the scopolamine-induced deficits. When administered in combination with scopolamine, apamin at 0.4 mg/kg significantly decreased the number of trials completed and increased the intertrial interval relative to that of the control group. Taken together, these results demonstrate that K+ channel blockers (4-AP and apamin), unlike a cholinesterase inhibitor (E2020), fail to reverse the scopolamine-induced deficits in the DMTP task.

摘要

研究了毒蕈碱拮抗剂氢溴酸东莨菪碱和甲基东莨菪碱、胆碱酯酶抑制剂E2020以及钾通道阻滞剂4-氨基吡啶(4-AP)和蜂毒明肽对大鼠在延迟位置匹配(DMTP)任务中表现的影响。测量了正确选择的百分比(选择准确率)、完成的试验次数和试验间隔。还使用信号检测分析计算了辨别力和反应偏差。氢溴酸东莨菪碱(0.1mg/kg),而非甲基东莨菪碱(0.1mg/kg),显著且持续降低了选择准确率和辨别力,但对其他测量指标均无影响。E2020(0.03 - 1.0mg/kg)对DMTP任务的基线表现无影响,但在1.0mg/kg时,它显著减轻了由东莨菪碱引起的选择准确率缺陷。4-AP(0.001 - 0.1mg/kg)对基线表现或东莨菪碱引起的缺陷均无影响。蜂毒明肽(0.1 - 0.4mg/kg)对选择准确率和辨别力无影响。蜂毒明肽也未能减轻东莨菪碱引起的缺陷。当与东莨菪碱联合给药时,0.4mg/kg的蜂毒明肽相对于对照组显著减少了完成的试验次数并增加了试验间隔。综上所述,这些结果表明,与胆碱酯酶抑制剂(E2020)不同,钾通道阻滞剂(4-AP和蜂毒明肽)无法逆转东莨菪碱在DMTP任务中引起的缺陷。

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