Yoburn B C, Kreuscher S P, Inturrisi C E, Sierra V
Department of Pharmaceutical Sciences, College of Pharmacy & Allied Health Professions, St. John's University, Jamaica, NY 11439.
Pharmacol Biochem Behav. 1989 Mar;32(3):727-31. doi: 10.1016/0091-3057(89)90025-7.
Mice of the Swiss-Webster strain obtained from two suppliers (Taconic, Charles River) were found to differ in their sensitivity to morphine. Mice from Taconic were approximately two-fold more sensitive to the analgesic and lethal effects of morphine compared to the Charles River mice. In a third strain, C3H/HEN, morphine was found to be more than 2.5 times more potent in producing analgesia than in the Charles River mice. Binding studies showed that the Taconic mice and C3H/HEN mice had approximately 40% and 60%, respectively, more specific [3H]naloxone binding sites in brain than did the less sensitive Charles River mice. When treated with chronic naltrexone for 8 days the analgesic potency of morphine was increased by approximately 90% for both Swiss-Webster mice and by 20% for the C3H/HENs. [3H]Naloxone binding was increased by 45-50% in the Swiss-Webster strains, but by only 33% in C3H/HEN mice. These data indicate that receptor upregulation is directly related to increases in morphine potency. Further, these findings suggest that initial sensitivity to morphine can determine the degree of functional supersensitivity and relative receptor upregulation produced by chronic opioid antagonist treatment.
从两家供应商（塔康尼克公司、查尔斯河公司）获得的瑞士-韦伯斯特品系小鼠对吗啡的敏感性存在差异。与查尔斯河小鼠相比，来自塔康尼克公司的小鼠对吗啡的镇痛和致死作用的敏感性大约高出两倍。在第三个品系C3H/HEN中，发现吗啡产生镇痛作用的效力比查尔斯河小鼠高出2.5倍以上。结合研究表明，与敏感性较低的查尔斯河小鼠相比，塔康尼克小鼠和C3H/HEN小鼠大脑中特异性[3H]纳洛酮结合位点分别多出约40%和60%。用慢性纳曲酮治疗8天后，瑞士-韦伯斯特小鼠和C3H/HEN小鼠的吗啡镇痛效力均提高了约90%，而C3H/HEN小鼠仅提高了20%。[3H]纳洛酮结合在瑞士-韦伯斯特品系中增加了45 - 50%，但在C3H/HEN小鼠中仅增加了33%。这些数据表明受体上调与吗啡效力的增加直接相关。此外，这些发现表明对吗啡的初始敏感性可以决定慢性阿片类拮抗剂治疗产生的功能超敏反应程度和相对受体上调情况。
