Maeda Takehiko, Kishioka Shiroh, Inoue Norihiro, Shimizu Norifumi, Fukazawa Yohji, Ozaki Masanobu, Yamamoto Hiroyuki
Department of Pharmacology, Wakayama Medical University, Japan.
Jpn J Pharmacol. 2002 Nov;90(3):270-5. doi: 10.1254/jjp.90.270.
This paper is the first report of a genetic index for morphine withdrawal in infant rats. We examined the effects of naloxone (2 mg/kg) on c-fos mRNA levels in brains of infant and adult rats following repeated treatment with morphine (20 mg/kg, once daily for 5 days). One hour after a single administration of naloxone (naloxone challenge), an increase in c-fos mRNA was observed in the olfactory bulb, hypothalamus and medulla oblongata of infant rats, and in the olfactory bulb and hypothalamus, but not in the medulla oblongata of adult rats. The c-fos mRNA levels returned to control levels 6 h after the naloxone challenge. The increase in c-fos mRNA levels was followed by body weight loss in both infant and adult rats. When MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, was co-administered along with morphine, it inhibited the naloxone-induced increases in c-fos mRNA levels in infant rats following repeated morphine administration. These results suggest that physical dependence develops in infant rats following repeated morphine administration and that the increment of c-fos mRNA levels is a useful indicator for naloxone-precipitated morphine withdrawal in infant as well as in adult rats.
本文首次报道了幼鼠吗啡戒断的遗传指标。我们研究了纳洛酮（2mg/kg）对反复给予吗啡（20mg/kg，每日一次，共5天）后的幼鼠和成年鼠大脑中c-fos mRNA水平的影响。单次给予纳洛酮（纳洛酮激发）1小时后，在幼鼠的嗅球、下丘脑和延髓中观察到c-fos mRNA增加，在成年鼠的嗅球和下丘脑中也有增加，但在成年鼠的延髓中未观察到。纳洛酮激发6小时后，c-fos mRNA水平恢复到对照水平。c-fos mRNA水平升高后，幼鼠和成年鼠的体重均下降。当非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂MK-801与吗啡同时给药时，它抑制了反复给予吗啡后幼鼠中纳洛酮诱导的c-fos mRNA水平升高。这些结果表明，反复给予吗啡后幼鼠会产生身体依赖性，并且c-fos mRNA水平的增加是幼鼠和成年鼠中纳洛酮诱发的吗啡戒断的有用指标。
