Fleetwood S W, Holtzman S G
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322.
Neuropharmacology. 1989 Jun;28(6):563-7. doi: 10.1016/0028-3908(89)90134-2.
This study was designed to evaluate whether or not rats that were tolerant to the analgesic action of morphine were also tolerant to stress-induced potentiation of morphine-induced analgesia. Rats were trained to drink either solutions of morphine (0.5 mg/ml) or drug-free tap water on a limited access schedule (10 min every 6 hr). The daily intake of morphine averaged 46 mg/kg. Nontolerant and rats tolerant to morphine were tested for morphine-induced analgesia (tail-flick assay), while either unstressed or stressed (i.e. immobilized in Plexiglas cylinders). Morphine produced dose- and time-dependent increases in tail-flick latencies in all groups. Increased sensitivity to analgesia induced by morphine was evident for both nontolerant and tolerant, stressed rats, when compared to their unstressed counterparts. Stress-induced potentiation of morphine-induced analgesia was characterized by dose-related increases in the peak effect and duration of the effect. Stress potentiated the analgesic effect of morphine, comparably in nontolerant (1.7-fold) and tolerant (1.5-fold) rats. Differential tolerance to analgesia induced by morphine and to stress-induced potentiation of morphine-induced analgesia suggests that different mechanisms mediate these two effects.
本研究旨在评估对吗啡镇痛作用产生耐受的大鼠是否也对压力诱导的吗啡镇痛增强作用产生耐受。大鼠在限时饮水方案（每6小时10分钟）下被训练饮用吗啡溶液（0.5毫克/毫升）或无药的自来水。吗啡的每日摄入量平均为46毫克/千克。对未耐受和耐受吗啡的大鼠进行吗啡诱导的镇痛测试（甩尾试验），同时分为未应激组或应激组（即固定在有机玻璃圆筒中）。吗啡在所有组中均产生剂量和时间依赖性的甩尾潜伏期增加。与未应激的对应大鼠相比，未耐受和耐受吗啡的应激大鼠对吗啡诱导的镇痛作用的敏感性均明显增加。压力诱导的吗啡镇痛增强作用的特征是峰值效应和效应持续时间的剂量相关增加。压力增强了吗啡的镇痛作用，在未耐受大鼠（1.7倍）和耐受大鼠（1.5倍）中相当。对吗啡诱导的镇痛作用和压力诱导的吗啡镇痛增强作用的差异耐受性表明，不同的机制介导了这两种效应。
