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吗啡对松鼠猴的辨别效应。

Discriminative effects of morphine in the squirrel monkey.

作者信息

Schaefer G J, Holzman S G

出版信息

J Pharmacol Exp Ther. 1977 Apr;201(1):67-75.

PMID:15105
Abstract

Squirrel monkeys were trained in a two-choice discrete trial avoidance task to discriminate between intramuscular injections of saline and 3.0 mg/kg of morphine. Morphine (0.1-10 mg/kg) produced a dose-related increase in the number of trials completed on the morphine-appropriate lever. The stimulus control produced by the discriminative effects of morphine met the following criteria for classification as a specific narcotic effect: 1) morphine-like stimulus control was produced by all other narcotic analgesics tested (fentanyl, oxymorphone, levorphanol, methadone and meperidine); 2) in so doing, these drugs spanned a 900-fold potency range relative to morphine; 3) stimulus control was blocked by the specific narcotic antagonist naloxone; and 4) stereospecificity was a requirement for stimulus control--levorphanol produced stimulus control equivalent to 3.0 mg/kg of mrophine but its optical isomer dextrorphan did not. The time course of the stimulus control produced by 3.0 mg/kg of morphine showed that the animals continued to respond on the morphine-appropriate lever up to 14 hours after morphine administration. In contrast, monkeys administered 0.01 mg/kg of fentanyl responded on the morphine lever for only as lone as 1/2 hour after fentanyl administration. Naloxone, d-amphetamine and pentobarbital all failed to substitute for morphine, Thus, this study has extended previous observations of the discriminative properties of morphine in rats by demonstrating that qualitatively similar data are produced in a second species, the squirrel monkey.

摘要

松鼠猴接受了一项双选离散试验回避任务的训练,以区分肌肉注射生理盐水和3.0毫克/千克吗啡。吗啡(0.1 - 10毫克/千克)使在与吗啡匹配的杠杆上完成的试验次数呈剂量相关增加。吗啡的辨别效应所产生的刺激控制符合以下作为特定麻醉效应分类的标准:1)所有其他测试的麻醉性镇痛药(芬太尼、羟吗啡酮、左啡诺、美沙酮和哌替啶)都产生了类似吗啡的刺激控制;2)在此过程中,这些药物相对于吗啡的效价范围跨越了900倍;3)刺激控制被特定的麻醉拮抗剂纳洛酮阻断;4)刺激控制需要立体特异性——左啡诺产生的刺激控制等同于3.0毫克/千克吗啡,但其光学异构体右啡烷则不然。3.0毫克/千克吗啡产生的刺激控制的时间进程表明,动物在吗啡给药后长达14小时内继续在与吗啡匹配的杠杆上做出反应。相比之下,给予0.01毫克/千克芬太尼的猴子在芬太尼给药后仅在吗啡杠杆上反应了半小时。纳洛酮、右旋苯丙胺和戊巴比妥都不能替代吗啡。因此,本研究通过证明在第二个物种松鼠猴中产生了定性相似的数据,扩展了先前对大鼠吗啡辨别特性的观察。

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