Raffa R B, Vaught J L, Setler P E
Department of Biological Research, Janssen Research Foundation, Spring House, PA 19477-0776.
Naunyn Schmiedebergs Arch Pharmacol. 1990 Nov;342(5):613-5. doi: 10.1007/BF00169053.
Rats were injected intraperitoneally with loreclezole (R 72063), diazepam, or scopolamine 60 min prior to acquisition of a passive avoidance task and tested 18 h later for retention of the learned (passive) behavior. The known impairment of performance produced by diazepam in this test is believed to be a model for the clinically observed diazepam-induced anterograde amnesia in humans. We report in this study that (1) consistent with the literature, pretreatment with diazepam (2.0-16.0 mg/kg i.p.) or scopolamine (3.0 mg/kg i.p.) produced impairment in passive avoidance performance of rats (anterograde amnesia), but (2) pretreatment with loreclezole (R 72063) (2.0-80.0 mg/kg i.p.) did not impair the acquisition, retention, or the retrieval (tested 18 h later) of passive avoidance behavior by rats at any dose. The results suggest that the anticonvulsant activity of loreclezole is mediated by a mechanism distinct from the one coupled to diazepam-like disruption of cognitive functions involved in the acquisition or posttraining information processing of passive avoidance behavior.
在大鼠习得被动回避任务前60分钟,经腹腔注射洛来唑(R 72063)、地西泮或东莨菪碱,18小时后测试其对所学(被动)行为的记忆保持情况。在该测试中,地西泮导致的已知行为表现受损被认为是临床上观察到的地西泮诱导的人类顺行性遗忘的模型。我们在本研究中报告:(1)与文献一致,地西泮(2.0 - 16.0毫克/千克,腹腔注射)或东莨菪碱(3.0毫克/千克,腹腔注射)预处理会导致大鼠被动回避行为表现受损(顺行性遗忘),但(2)洛来唑(R 72063)(2.0 - 80.0毫克/千克,腹腔注射)预处理在任何剂量下均不会损害大鼠被动回避行为的习得、记忆保持或回忆(18小时后测试)。结果表明,洛来唑的抗惊厥活性是由一种不同于与地西泮样干扰被动回避行为习得或训练后信息处理中认知功能相关的机制介导的。