Mucha R F, Kalant H
Psychopharmacology (Berl). 1981;75(2):132-3. doi: 10.1007/BF00432174.
Male wistar rats, previously made tolerant to morphine by at least 3 weeks of daily intraperitoneal (IP) injections of 20 mg/kg morphine-SO4 (MS), were then given 200 mg/kg MS daily for 4 or 5 days. Tail immersion tests of antinociception, carried out before and after the 200 mg/kg MS treatment, indicated that the additional morphine treatment, was followed by a large further decrease in opiate sensitivity, characterized by decreased slope of the log-dose/response curve (LDR curve flattening). The further decrease in opiate sensitivity was substantially reduced by naloxone-HCl (IP) in a dose of 10 mg/kg given 30 min before and 8 h after the 200 mg/kg MS injections, or a dose of 4 mg/kg given 45 min after the MS. It was concluded that LDR curve flattening produced by high doses of MS is mediated by specific opiate receptors, and is a true expression of a high degree of opiate tolerance in the intact rat.
雄性Wistar大鼠，此前通过每日腹腔注射20 mg/kg硫酸吗啡（MS）至少3周已对吗啡产生耐受性，随后连续4或5天每天给予200 mg/kg MS。在200 mg/kg MS治疗前后进行的尾部浸没法抗伤害感受测试表明，额外的吗啡治疗后，阿片类药物敏感性大幅进一步降低，其特征为对数剂量/反应曲线斜率降低（LDR曲线变平）。在200 mg/kg MS注射前30分钟和注射后8小时给予10 mg/kg剂量的盐酸纳洛酮（腹腔注射），或在MS注射后45分钟给予4 mg/kg剂量的盐酸纳洛酮，可使阿片类药物敏感性的进一步降低显著减轻。得出的结论是，高剂量MS导致的LDR曲线变平是由特定的阿片受体介导的，并且是完整大鼠高度阿片耐受性的真实表现。
