Kirby M L, Holtzmann S G
Pharmacol Biochem Behav. 1982 Feb;16(2):263-9. doi: 10.1016/0091-3057(82)90159-9.
No studies have been reported previously on fetal behavior after chronic morphine administration during the period of opiate receptor ontogenesis. In the present study, pregnant rats were injected with 20 mg/kg/day divided into either two or four daily doses. The injections were made from day 12 through the end of gestation. On days 18-20, the effect of morphine and naloxone on fetal activity in the pretreated animals was assessed by visual observation and quantification. Animals exposed twice daily to morphine showed a morphine-induced depression in spontaneous activity similar to animals pretreated with saline while animals injected four times daily developed tolerance to the depressant effect of the morphine. Animals injected with either morphine or levorphanol were hyperactive after challenge with naloxone. Animals injected with saline or dextrorphan or pair-fed were not hyperactive after exposure to naloxone. Even though behavioral changes were seen in utero after injection of morphine, 30-day neonates which had been treated identically prenatally did not show changes in the analgesic response to morphine.
此前尚无关于在阿片受体发生期慢性给予吗啡后胎儿行为的研究报道。在本研究中,将怀孕大鼠按20mg/kg/天的剂量注射吗啡,分为每日两次或四次给药。从妊娠第12天开始注射直至妊娠结束。在第18 - 20天,通过视觉观察和定量评估吗啡和纳洛酮对预处理动物胎儿活动的影响。每天接受两次吗啡注射的动物表现出与生理盐水预处理动物相似的吗啡诱导的自发活动抑制,而每天注射四次吗啡的动物则对吗啡的抑制作用产生了耐受性。注射吗啡或左啡诺的动物在接受纳洛酮激发后表现为活动亢进。注射生理盐水、右啡烷或配对喂养的动物在接触纳洛酮后未出现活动亢进。尽管注射吗啡后在子宫内观察到行为变化,但产前接受相同处理的30日龄新生儿对吗啡的镇痛反应并未出现变化。