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钾通道调节剂对小鼠认知过程的影响。

Influence of potassium channel modulators on cognitive processes in mice.

作者信息

Ghelardini C, Galeotti N, Bartolini A

机构信息

Department of Preclinical and Clinical Pharmacology, Florence, Italy.

出版信息

Br J Pharmacol. 1998 Mar;123(6):1079-84. doi: 10.1038/sj.bjp.0701709.

Abstract
  1. The effect of i.c.v. administration of different potassium channel openers (minoxidil, pinacidil, cromakalim) and potassium channel blockers (tetraethylammonium, apamin, charybdotoxin, gliquidone, glibenclamide) on memory processes was evaluated in the mouse passive avoidance test. 2. The administration of minoxidil (10 microg per mouse i.c.v.), pinacidil (5-25 microg per mouse i.c.v.) and cromakalim (10-25 microg per mouse i.c.v.) immediately after the training session produced an amnesic effect. 3. Tetraethylammonium (TEA; 1-5 microg per mouse i.c.v.), apamin (10 ng per mouse i.c.v.), charybdotoxin (1 microg per mouse i.c.v.), gliquidone (3 microg per mouse i.c.v.) and glibenclamide (1 microg per mouse i.c.v.), administered 20 min before the training session, prevented the potassium channel opener-induced amnesia. 4. At the highest effective doses, none of the drugs impaired motor coordination, as revealed by the rota rod test, or modified spontaneous motility and inspection activity, as revealed by the hole board test. 5. These results suggest that the modulation of potassium channels plays an important role in the regulation of memory processes. On this basis, the potassium channel blockers could be useful in the treatment of cognitive deficits.
摘要
  1. 在小鼠被动回避试验中评估了脑室内注射不同钾通道开放剂(米诺地尔、匹那地尔、克罗卡林)和钾通道阻滞剂(四乙铵、蜂毒明肽、大蝎毒素、格列喹酮、格列本脲)对记忆过程的影响。2. 训练后立即注射米诺地尔(每只小鼠脑室内注射10微克)、匹那地尔(每只小鼠脑室内注射5 - 25微克)和克罗卡林(每只小鼠脑室内注射10 - 25微克)会产生遗忘效应。3. 在训练前20分钟注射四乙铵(TEA;每只小鼠脑室内注射1 - 5微克)、蜂毒明肽(每只小鼠脑室内注射10纳克)、大蝎毒素(每只小鼠脑室内注射1微克)、格列喹酮(每只小鼠脑室内注射3微克)和格列本脲(每只小鼠脑室内注射1微克)可预防钾通道开放剂诱导的遗忘。4. 在最高有效剂量下,如旋转棒试验所示,这些药物均未损害运动协调性,如洞板试验所示,也未改变自发运动和探究活动。5. 这些结果表明钾通道的调节在记忆过程的调控中起重要作用。在此基础上,钾通道阻滞剂可能对治疗认知缺陷有用。

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