Effects of benzodiazepine receptor inverse agonists and nicotine on behavioral vigilance in senescent rats.
Effects of benzodiazepine receptor inverse agonists and nicotine on behavioral vigilance in senescent rats.
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苯二氮卓受体反向激动剂和尼古丁对衰老大鼠行为警觉性的影响。
DOI：
10.1093/gerona/51a.3.b225
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Sarter,M
中科院分区：
文献类型：
--
作者：
Turchi,J;Holley,LA;Sarter,M
先前的实验表明，与6个月大的大鼠相比，20个月大的大鼠在行为警戒任务中的表现的特征在于其检测简短视觉信号的能力受损，而其区分较长信号和非信号事件的能力不受影响。苯二氮卓类受体（BZR）激动剂氯氮卓有效地和选择性地相互作用的相对命中数的年龄的影响。然而，GABA能传递的负调节剂（ZK 93 426，β-CCtB，RU 33965）未能减弱年龄对行为警觉性的影响。本实验检验了衰老动物（28个月）的性能进一步受损的假设，因此可以证明BZR反向激动剂或尼古丁的有益作用。然而，ZK 93 426的施用（0.39、1.56、6.25 mg/kg），RU 33965（0.1、0.5毫克/千克）或尼古丁（0.09、0.287、0.689 mg/kg）对衰老动物的性能没有有利影响;考虑到这些化合物在具有实验诱导的胆碱能功能损伤的动物中的有益行为作用，本发明的发现指出了在关于BZR反向激动剂或尼古丁诱导的由胆碱能功能减退引起的认知损伤的减弱的动物实验中，正常衰老作为变量的局限性。
Previous experiments demonstrated that, compared with 6-month-old rats, the performance of 20-month-old rats in a behavioral vigilance task was characterized by an impairment in their ability to detect brief visual signals, whereas their ability to discriminate between longer signals and nonsignal events was unaffected. The benzodiazepine receptor (BZR) agonist chlordiazepoxide potently and selectively interacted with the effects of age on the relative number of hits. However, negative modulators of GABAergic transmission (ZK 93 426, β-CCtB, RU 33965) failed to attenuate the effects of age on behavioral vigilance. The present experiment tested the hypothesis that the performance of senescent animals (28 months) is further impaired and thus would allow the demonstration of beneficial effects of BZR inverse agonists or nicotine. However, administration of ZK 93 426 (0.39, 1.56, 6.25 mg/kg), RU 33965 (0.1, 0.5 mgl kg), or nicotine (0.09, 0.287, 0.689 mg/kg) did not beneficially affect the performance of senescent animals; rather, detrimental effects were found. Considering the beneficial behavioral effects of these compounds in animals with experimentally induced impairments in cholinergic function, the present findings point to limitations of normal aging as a variable in animal experiments on BZR inverse agonist or nicotine-induced attenuation of cognitive impairments that result from cholinergic hypofunction.