Ohno M, Yamamoto T, Watanabe S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Eur J Pharmacol. 1992 Aug 25;219(2):245-51. doi: 10.1016/0014-2999(92)90302-k.
In a three-panel runway task, the benzodiazepine chlordiazepoxide at 3.2 and 10 mg/kg i.p. significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) in a test of working memory, but it had no effect on errors in a test of reference memory. This effect of 10 mg/kg chlordiazepoxide on working memory was blocked by the benzodiazepine receptor antagonist flumazenil at 10 mg/kg. Intrahippocampal injection of chlordiazepoxide at 10 and 32 micrograms/side significantly increased the number of working memory errors. This effect of intrahippocampal chlordiazepoxide (32 micrograms/side) was attenuated not only by flumazenil at 10 mg/kg but also by the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline at 3.2 mg/kg. Intrahippocampal injection of the GABAA receptor agonist muscimol at 100 and 320 ng/side also significantly increased working memory errors. Neither chlordiazepoxide nor muscimol affected the number of reference memory errors when injected into the hippocampus at doses up to 32 micrograms/side or 320 ng/side, respectively. These results suggest that activation of the GABAA/benzodiazepine receptor complex in the hippocampus impairs working memory, but does not affect reference memory.
在一项三面板跑道任务中，腹腔注射3.2毫克/千克和10毫克/千克的苯二氮䓬类药物氯氮䓬，在工作记忆测试中显著增加了错误数量（在四个选择点尝试通过三个面板门中的两个错误面板），但对参考记忆测试中的错误没有影响。10毫克/千克氯氮䓬对工作记忆的这种影响被10毫克/千克的苯二氮䓬受体拮抗剂氟马西尼阻断。海马内注射10微克/侧和32微克/侧的氯氮䓬显著增加了工作记忆错误的数量。海马内注射氯氮䓬（32微克/侧）的这种影响不仅被10毫克/千克的氟马西尼减弱，还被3.2毫克/千克的γ-氨基丁酸（GABA）A受体拮抗剂荷包牡丹碱减弱。海马内注射100纳克/侧和320纳克/侧的GABAA受体激动剂蝇蕈醇也显著增加了工作记忆错误。当分别以高达32微克/侧或320纳克/侧的剂量注入海马时，氯氮䓬和蝇蕈醇均不影响参考记忆错误的数量。这些结果表明，海马中GABAA/苯二氮䓬受体复合物的激活会损害工作记忆，但不影响参考记忆。
