Attenuation of morphine tolerance and withdrawal syndrome by coadministration of nalbuphine |
| |
Authors: | Soyong Jang Heejeong Kim Donghyun Kim Myeon Woo Jeong Tangen Ma Seongyoul Kim Ing K Ho Seikwan Oh |
| |
Institution: | (1) Department of Neuroscience, College of Medicine, Ewha Womans University, Mok-dong, Yangchon-ku, 158-710 Seoul, Korea;(2) Medical Research Institute, College of Medicine, Ewha Womans University, Mok-dong, Yangchon-ku, 158-710 Seoul, Korea;(3) Department of Pharmacology, National Institute of Toxicological Research, KFDA, 122-704 Seoul, Korea;(4) Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 39216 Jackson, MS, USA |
| |
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. |
| |
Keywords: | Morphine Nalbuphine Tolerance μ receptor κ receptor Autoradiography |
本文献已被 PubMed SpringerLink 等数据库收录! |
|