Hoffmann O, Wiesenfeld-Hallin Z
Karolinska Institute, Department of Medical Laboratory Sciences and Technology, Huddinge University Hospital, Sweden.
Neuroreport. 1994 Dec 20;5(18):2565-8. doi: 10.1097/00001756-199412000-00040.
The ability of the selective cholecystokinin-B (CCK-B) receptor antagonist Cl 988 to reverse tolerance to morphine's antinociceptive effect was investigated with the hot-plate test in Sprague-Dawley rats. Tolerance was induced by subcutaneous (s.c.) injection of 10 mg kg-1 morphine twice daily for four days. On the fifth day rats were administered CI 988 (10 mg kg-1) or saline plus 5 mg kg-1 morphine s.c. Significant antinociception was observed in the group that received the CCK-B antagonist plus morphine, whereas the saline plus morphine group exhibited total tolerance. These results suggest that upregulation of the endogenous CCK system during repeated morphine administration may have an important role in the development of opiate tolerance.
利用热板试验，在斯普拉格-道利大鼠中研究了选择性胆囊收缩素B（CCK-B）受体拮抗剂CI 988逆转对吗啡镇痛作用耐受性的能力。通过每天皮下注射（s.c.）10 mg/kg吗啡，连续四天诱导耐受性。在第五天，给大鼠注射CI 988（10 mg/kg）或生理盐水加5 mg/kg吗啡皮下注射。在接受CCK-B拮抗剂加吗啡的组中观察到显著的镇痛作用，而生理盐水加吗啡组则表现出完全耐受性。这些结果表明，反复给予吗啡期间内源性CCK系统的上调可能在阿片类药物耐受性的发展中起重要作用。
