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The Development of Tolerance to and Dependence on Morphine are Reduced by Co-administration of Nalbuphine in Rat  

정면우 (국립독성연구원 약리부)
임화경 (국립독성연구원 약리부)
전용준 (국립독성연구원 약리부)
김혜정 (국립독성연구원 약리부)
박인숙 (국립독성연구원 약리부)
오우용 (국립독성연구원 약리부)
왕소영 (국립독성연구원 약리부)
박윤주 (국립독성연구원 약리부)
강주희 (국립독성연구원 약리부)
Publication Information
YAKHAK HOEJI / v.46, no.4, 2002 , pp. 276-282 More about this Journal
Abstract
Morphine has been used widely on the treatment of many types of chronic pain. However the development of tolerance to morphine by repeat application is a major problem in pain therapy. The purpose of the present study was to investigate whether combined administration of nalbuphine with morphine affects the development of tolerance to and dependence on morphine. We hypothesize that the use of nalbuphine, k-agonist may prove to be useful adjunct therapy to prevent morphine-induced undesirable effects in the management of some forms of chronic pain. Morphine (10 mg/kg) was injected to rats intraperitoneally for 5 days. The variable dose of nalbuphine (0.1, 1.0 and 5.0 mg/kg) was administered (i.p.) in combination with morphine injection. The development of tolerance to morphine was assessed by measuring the antinociceptive effect with the Randall-Selitto apparatus. The development of dependence on morphine was determined by the scoring the precipitated withdrawal signs for 20 min after injection of naloxone (10 mg/kg, i.p.). Nalbuphine did not attenuate antinociceptive effect of morphine in rats. Interestingly, combined administration of morphine with nalbuphine (100:1) significantly attenuated the development of morphine tolerance and dependence. These results suggest that the co-administration of nalbuphine with morphine in chronic morphine treatment can be one of therapies to reduce the development of dependence on morphine.
Keywords
Morphine; nalbuphine; tolerance; dependence;
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