Fanselow M S, Cramer C P
Department of Psychology, Dartmouth College, Hanover, NH 03755.
Pharmacol Biochem Behav. 1988 Oct;31(2):431-8. doi: 10.1016/0091-3057(88)90370-x.
The acquisition of morphine analgesic tolerance was investigated in neonatal rats. Morphine was found to produce a potent analgesia, as measured by latency to retract a hindpaw from a 52 degree C hotplate, in rat pups as young as 1 day of age. Morphine analgesic tolerance, however, did not develop in rats until the third week of life. Rats given the same daily morphine regimen starting at 15 days of age or older showed rapid tolerance development. The data from four experiments indicate that experience with morphine prior to this age (Day 15) does not impact on the analgesic efficacy of the drug. Similarly, when morphine treatment was discontinued and the rats given a naloxone challenge, withdrawal symptoms were not observed in very young rats. Opiate withdrawal was first detected in rats that started their daily morphine treatment at 30 days of age and were then challenged with naloxone at 52 days of age. Therefore, two correlates of opiate addiction, tolerance and withdrawal, appear to be relatively late-developing phenomena in the rat.
在新生大鼠中研究了吗啡镇痛耐受性的获得情况。通过观察大鼠幼崽从52摄氏度热板上缩回后爪的潜伏期来衡量，发现吗啡对1日龄的幼鼠就能产生强效镇痛作用。然而，大鼠直到出生后第三周才会出现吗啡镇痛耐受性。从15日龄及以上开始给予相同每日吗啡给药方案的大鼠表现出快速的耐受性发展。来自四项实验的数据表明，在此年龄（第15天）之前接触吗啡不会影响该药物的镇痛效果。同样，当停止吗啡治疗并对大鼠进行纳洛酮激发试验时，非常年幼的大鼠未观察到戒断症状。阿片类药物戒断症状首次在30日龄开始每日接受吗啡治疗、52日龄接受纳洛酮激发试验的大鼠中被检测到。因此，阿片类药物成瘾的两个相关因素，耐受性和戒断症状，在大鼠中似乎是相对较晚出现的现象。
