Thorat S N, Bhargava H N
Department of Pharmaceutics and Pharmacodynamics, University of Illinois at Chicago 60612.
Eur J Pharmacol. 1994 Jul 21;260(1):5-13. doi: 10.1016/0014-2999(94)90003-5.
Male Swiss-Webster mice were rendered tolerant to morphine by subcutaneous implantation of a morphine pellet, each containing 75 mg morphine base, for 3 days. Mice implanted with placebo pellets served as controls. A high degree of tolerance to the analgesic effect of morphine developed as evidenced by decreased analgesic response to various doses of morphine. delta 9-Tetrahydrocannabinol (5, 10 and 20 mg/kg i.p.) produced dose-dependent analgesic and hypothermic effects in mice implanted with placebo pellets. A significant decrease in the analgesic effects of tetrahydrocannabinol was observed in morphine-tolerant mice as compared to placebo controls. Mice were rendered tolerant to delta 9-tetrahydrocannabinol by injecting the drug (5, 10, or 20 mg/kg i.p.) twice daily for 4 days. Vehicle-injected mice served as controls. Tolerance to the analgesic and hypothermic effects of delta 9-tetrahydrocannabinol in mice injected chronically with the drug was evidenced by the decreases in the intensity of these responses when compared to those observed in vehicle-injected controls. Morphine produced dose-dependent analgesic and hypothermic effects in mice injected chronically with vehicle but the intensity of these effects was significantly lower in mice injected chronically with delta 9-tetrahydrocannabinol. These results indicate that a possible interaction exists between delta 9-tetrahydrocannabinol and the mu-opioid receptors and that a substantial tolerance to analgesic and hypothermic effects of morphine develops in delta 9-tetrahydrocannabinol-tolerant mice.(ABSTRACT TRUNCATED AT 250 WORDS)
通过皮下植入每粒含75毫克吗啡碱的吗啡丸3天，使雄性瑞士韦伯斯特小鼠对吗啡产生耐受性。植入安慰剂丸的小鼠作为对照。对各种剂量吗啡的镇痛反应降低表明，小鼠对吗啡的镇痛作用产生了高度耐受性。δ9-四氢大麻酚（腹腔注射5、10和20毫克/千克）在植入安慰剂丸的小鼠中产生剂量依赖性的镇痛和体温降低作用。与安慰剂对照相比，在吗啡耐受小鼠中观察到四氢大麻酚的镇痛作用显著降低。通过每天两次注射药物（腹腔注射5、10或20毫克/千克），持续4天，使小鼠对δ9-四氢大麻酚产生耐受性。注射溶媒的小鼠作为对照。与注射溶媒的对照小鼠相比，长期注射该药物的小鼠对δ9-四氢大麻酚的镇痛和体温降低作用的耐受性表现为这些反应强度的降低。吗啡在长期注射溶媒的小鼠中产生剂量依赖性的镇痛和体温降低作用，但在长期注射δ9-四氢大麻酚的小鼠中，这些作用的强度显著较低。这些结果表明，δ9-四氢大麻酚与μ阿片受体之间可能存在相互作用，并且在δ9-四氢大麻酚耐受的小鼠中对吗啡的镇痛和体温降低作用产生了显著耐受性。（摘要截短为250字）
