Ro 15-1788 antagonizes the discriminative stimulus effects of diazepam in rats but not similar effects of pentobarbital.
Ro 15-1788 antagonizes the discriminative stimulus effects of diazepam in rats but not similar effects of pentobarbital.
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DOI：
10.1016/0024-3205(82)90102-3
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发表时间：
1982-11
期刊：
影响因子：
6.1
通讯作者：
S. Herling;H. Shannon
中科院分区：
文献类型：
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作者：
S. Herling;H. Shannon
在接受过训练的大鼠中评价了Ro 15-1788的苯二氮卓类拮抗剂特性，以在两种选择的离散试验休克避免程序中区分生理盐水和1.0 mg/kg地西泮或10 mg/kg戊巴比妥。当单独给药时，1.0 mg/kg地西泮和10 mg/kg戊巴比妥产生相当数量的药物适当反应（> 84%），无论大鼠是否接受过区分地西泮或戊巴比妥和盐水的训练。Ro 15-1788（3-32 mg/kg，经口），在地西泮或戊巴比妥之前10分钟给药，对两组大鼠的地西泮辨别作用产生了剂量相关的阻断作用，但对阻断戊巴比妥的辨别作用完全无效。10和32 mg/kg Ro 15-1788分别使地西泮辨别作用的剂量-效应曲线以平行方式向右移动3倍和13倍，表明Ro 15-1788作为地西泮的可克服的竞争性拮抗剂。当单独施用时，Ro 15-1788（32-100 mg/kg，p.o.）主要产生生理盐水适当的反应，尽管100 mg/kg Ro 15-1788在八只大鼠中的一只中产生药物适当的反应。在地西泮给药后30分钟经口给药时，Ro 15-1788（32 mg/kg）在10分钟内完全逆转地西泮的辨别作用。32 mg/kg Ro 15-1788对地西泮辨别作用的阻断似乎至少持续与地西泮单独作用一样长的时间（约2小时）。
The benzodiazepine antagonist properties of Ro 15-1788 were evaluated in rats trained to discriminate between saline and either 1.0 mg/kg of diazepam or 10 mg/kg of pentobarbital in a two-choice discrete-trial shock avoidance procedure. When administered alone, 1.0 mg/kg of diazepam and 10 mg/kg of pentobarbital produced comparable amounts of drug-appropriate responding (> 84%), whether rats were trained to discriminate between diazepam or pentobarbital and saline. Ro 15-1788 (3–32 mg/kg, p.o.), administered 10 min before diazepam or pentobarbital, produced a dose-related blockade of the discriminative effects of diazepam in both groups of rats, but was completely ineffective in blocking the discriminative effects of pentobarbital. The dose-effect curve for the discriminative effects of diazepam was shifted to the right in a parallel fashion 3- and 13-fold by 10 and 32 mg/kg of Ro 15-1788, respectively, indicating that Ro 15-1788 acts as a surmountable, competitive antagonist of diazepam. When administered alone, Ro 15-1788 (32–100 mg/kg, p.o.) produced primarily saline-appropriate responding, although 100 mg/kg of Ro 15-1788 produced drug-appropriate responding in one out of eight rats. When administered orally 30 min after diazepam, Ro 15-1788 (32 mg/kg) completely reversed within 10 min the discriminative effects of diazepam. The blockade of diazepam's discriminative effects by 32 mg/kg of Ro 15-1788 appeared to last at least as long (approximately 2 hr) as the effects of diazepam alone.