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新型促甲状腺激素释放激素(TRH)类似物TA-0910的药理学研究(IV):对小鼠和大鼠实验性记忆损伤的影响

Pharmacological study of TA-0910, a new thyrotropin-releasing hormone (TRH) analog (IV): Effects on experimental memory impairment in mice and rats.

作者信息

Yamamura M, Kinoshita K, Nakagawa H, Ishida R

机构信息

Department of Pharmacology, Safety Research Laboratory, Osaka, Japan.

出版信息

Jpn J Pharmacol. 1991 Feb;55(2):241-53. doi: 10.1254/jjp.55.241.

Abstract

The effects of a new TRH analog, TA-0910, orally administered, on experimental memory impairments for the one-trial passive avoidance response in anoxic mice (light-dark box), active avoidance response in basal forebrain (BF)-lesioned rats (shuttle box), and delayed alternation task in scopolamine-treated rats (T-maze) were studied. In mice, TA-0910 (3-30 mg) administered 60 min before the retention trial dose-dependently prolonged the passive avoidance response latency reduced by CO2-exposure that was given immediately after the acquisition trial, but not when it was given 60 min before the acquisition or just after the anoxic treatment. In rats, TA-0910 (0.3-3 mg/kg) administered 40-60 min before the test trial, dose-dependently prevented the reduction in mean avoidance rate caused by BF-lesioning and elevated the scopolamine (0.1 mg/kg, i.p.)-induced reduction in percent correct choice level in the alternation task. TRH (30-300 mg/kg), on the other hand, produced no improvements in any of the above tests. These results suggest that TA-0910 improves impaired memory by correcting the retrieval process of memory.

摘要

研究了口服一种新型促甲状腺激素释放激素类似物TA - 0910,对缺氧小鼠(明暗箱)单次被动回避反应实验性记忆损伤、基底前脑(BF)损伤大鼠(穿梭箱)主动回避反应以及东莨菪碱处理大鼠(T迷宫)延迟交替任务的影响。在小鼠中,在记忆保持试验前60分钟给予TA - 0910(3 - 30毫克),剂量依赖性地延长了在获得性试验后立即给予的二氧化碳暴露所缩短的被动回避反应潜伏期,但在获得性试验前60分钟或缺氧处理后立即给予时则没有这种效果。在大鼠中,在测试试验前40 - 60分钟给予TA - 0910(0.3 - 3毫克/千克),剂量依赖性地防止了BF损伤导致的平均回避率降低,并提高了东莨菪碱(0.1毫克/千克,腹腔注射)诱导的交替任务中正确选择水平百分比的降低。另一方面,促甲状腺激素释放激素(30 - 300毫克/千克)在上述任何测试中均未产生改善作用。这些结果表明,TA - 0910通过纠正记忆的检索过程来改善受损记忆。

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