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Attenuation of morphine tolerance and withdrawal syndrome by coadministration of nalbuphine

Title
Attenuation of morphine tolerance and withdrawal syndrome by coadministration of nalbuphine
Authors
Jang S.Kim H.Kim D.Myeon W.J.Ma T.Kim S.Ho I.K.Oh S.
Ewha Authors
오세관
SCOPUS Author ID
오세관scopus
Issue Date
2006
Journal Title
Archives of Pharmacal Research
ISSN
0253-6269JCR Link
Citation
vol. 29, no. 8, pp. 677 - 684
Indexed
SCIE; SCOPUS; KCI WOS scopus
Abstract
Morphine has been used widely on the treatment of many types of chronic pain. However the development of tolerance to and dependence on 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, κ-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 day. 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 morphine tolerance 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 30 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 (10:1) significantly attenuated the development of dependence on morphine. The elevation of [ 3H]MK-801 binding in frontal cortex, dentate gyrus, and cerebellum after chronic morphine infusion was suppressed by the coadministration of nalbuphine. In addition, the elevation of NR1 expression by morphine was decreased by the coadministration of nalbuphine in rat cortex. These results suggest that the coadministration of nalbuphine with morphine in chronic pain treatment can be one of therapies to reduce the development of tolerance to and dependence on morphine.
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의학전문대학원 > 의학과 > Journal papers
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