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通过小鼠冲突试验和非匹配样本试验评估三种苯二氮䓬类药物(地西泮、阿普唑仑和三唑仑)的抗焦虑和遗忘作用。

Assessment of the anxiolytic and amnesic effects of three benzodiazepines, diazepam, alprazolam and triazolam, by conflict and non-matching to sample tests in mice.

作者信息

Kuribara H, Asahi T

机构信息

Department of Neurobiology and Behavior, Gunma University School of Medicine, Maebashi, Japan.

出版信息

Nihon Shinkei Seishin Yakurigaku Zasshi. 1997 Feb;17(1):1-6.

PMID:9134532
Abstract

The anti-conflict and amnesic effects of three benzodiazepines (diazepam, alprazolam and triazolam) po-administered in mice were assessed by a modified Geller Seifter conflict test and a non-matching to sample test using a 4-arm maze with 3 selectable arms, respectively. Diazepam (10 mg/kg), alprazolam (1-10 mg/kg) and triazolam (1 and 3 mg/kg) significantly increased the lever-press in the alarm period (punished responding) under the conflict test. Under the non-matching to sample test, the correct response (CR), but not non-reward response (NR), decreased depending on the delay time. Diazepam (3 mg/kg) significantly decreased the CR under 0-sec delay condition, but not that under 30-sec delay condition. Comparatively higher doses of the benzodiazepines, diazepam (10 mg/kg), alprazolam (1 and 3 mg/kg) and triazolam (0.3 and 1 mg/kg), significantly decreased the CR under both 0- and 30-sec delay conditions. However, no significant change in the NR was produced by any dose of the three benzodiazepines. These results suggest that the decrease in CR during the non-matching to sample test is caused by the impairment of cognitive function rather than working and reference memories, and that such effects appear at doses equal to and/or less than the effective doses for anti-conflict effect. However, the assumption that triazolam has the highest risk of induction of amnesia, as compared to the advantage of sleep induction or relief of anxiety in the benzodiazepine group, was not supported by the present results.

摘要

分别通过改良的盖勒-西弗冲突试验和使用具有3个可选臂的四臂迷宫的非匹配样本试验,评估了三种苯二氮䓬类药物(地西泮、阿普唑仑和三唑仑)经口给药对小鼠的抗冲突和遗忘作用。在冲突试验中,地西泮(10毫克/千克)、阿普唑仑(1 - 10毫克/千克)和三唑仑(1和3毫克/千克)显著增加了警报期(受惩罚反应)的压杆次数。在非匹配样本试验中,正确反应(CR)而非无奖励反应(NR)根据延迟时间而减少。地西泮(3毫克/千克)在0秒延迟条件下显著降低了CR,但在30秒延迟条件下未降低。相对较高剂量的苯二氮䓬类药物,地西泮(10毫克/千克)、阿普唑仑(1和3毫克/千克)和三唑仑(0.3和1毫克/千克),在0秒和30秒延迟条件下均显著降低了CR。然而,三种苯二氮䓬类药物的任何剂量均未使NR产生显著变化。这些结果表明,非匹配样本试验期间CR的降低是由认知功能受损而非工作记忆和参考记忆受损引起的,并且这种作用在等于和/或低于抗冲突作用有效剂量时出现。然而,本研究结果并不支持与苯二氮䓬类药物组中诱导睡眠或缓解焦虑的优势相比,三唑仑具有最高失忆诱导风险的假设。

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