Browse > Article

Attenuation of Morphine Tolerance and Withdrawal Syndrome by Coadministration of Nalbuphine  

Jang, So-Yong (Department of Neuroscience, College of Medicine, Ewha Womans University)
Kim, Hee-Jeong (Department of Neuroscience, College of Medicine, Ewha Womans University)
Kim, Dong-Hyun (Medical Research Institute, College of Medicine, Ewha Womans University)
Jeong, Myeon-Woo (Department of Pharmacology, National Institute of Toxicological Research, KFDA)
Ma, Tangen (Department of Pharmacology and Toxicology, University of Mississippi Medical Center)
Kim, Seong-Youl (Department of Pharmacology and Toxicology, University of Mississippi Medical Center)
Ho, Ing K. (Department of Pharmacology and Toxicology, University of Mississippi Medical Center)
Oh, Sei-Kwan (Department of Neuroscience, Medical Research Institute, College of Medicine, Ewha Womans University)
Publication Information
Archives of Pharmacal Research / v.29, no.8, 2006 , pp. 677-684 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 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, ${\kappa}-agonist$ 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; ${\mu}$ receptor; ${\kappa}$ receptor; Autoradiography;
Citations & Related Records

Times Cited By Web Of Science : 6  (Related Records In Web of Science)
Times Cited By SCOPUS : 4
연도 인용수 순위
1 Aceto, M. D., Dewey, W. L., Chang, J. K., and Lee, N. M., Dynorphin-(1-13): effects in nontolerant and morphinedependent rhesus monkeys. Eur. J. Pharmacol., 83, 139-142 (1982)   DOI   ScienceOn
2 Chen, J. C., Smith, E. R., Cahill, M., Cohen, R., and Fishman, J. R., The opioid receptor binding of pentazocine, morphine, fentanyl, butorphanol and nalbuphine. Life Sci., 52, 389-396 (1992)
3 Franklin, K. B. J. and Paxinos, G., The mouse brain in stereotaxic coordinates, Academic Press, San Diego, CA (1997)
4 Kayser, V. and Guilbaud, G., The analgesic effects of morphine but not those of the enkephalinase inhibitor thiorphan, are enhanced in arthritic rats. Brain Res., 267, 131-138 (1983)   DOI   ScienceOn
5 Pillai, N. P. and Ross, D. H., Interaction of kappa receptor agonists with $Ca^{2+}$ channel antagonists in the modulation of hypothermia. Eur. J. Pharmacol., 132, 237-244 (1986)   DOI   ScienceOn
6 Schmidt, W. K., Tam, S. W., Shotzberger, G. S., Smith, D. H. Jr, Clark, R., and Vernier, V. G., Nalbuphine. Drug Alcohol Depend., 14, 339-362 (1985)   DOI   ScienceOn
7 Tokuyama, S., Wakabayashi, H., and Ho, I. K., Direct evidence for a role of glutamate in the expression of the opioid withdrawal syndrome. Eur. J. Pharmacol., 295, 123-129 (1996)   DOI   ScienceOn
8 Tokuyama, S., Zhu, H., Oh, S., Ho, I. K., and Yamamoto, T., Further evidence for a role of NMDA receptors in the locus coeruleus in the expression of withdrawal syndrome from opioids. Neurochem. Int., 39, 103-109 (2001)   DOI   ScienceOn
9 Picker, M. J., Yarbrough, J., Hughes, C. E., Smith, M. A., Morgan, D., and Dykstra, L. A., Agonist and antagonist effect of mixed action opioids in the pigeon drug discrimininant procedure: influence of training dose, intrinsic efficacy and interanimal differences. J. Pharmacol. Exp. Ther., 266, 756- 767 (1993)
10 Narita, M. Opioid-regulated pharmacological interaction and intracellular signaling mechanism. Dissertation for Ph.D., Hoshi University, Tokyo, Japan (1992)
11 Sofuoglu, M., Portoghese, P. S., and Takemori, A. E., Maintenance of acute morphine tolerance in mice by selective blockage of kappa opioid receptors with norbinaltorphimine. Eur. J. Pharmacol., 210, 159-162 (1992)   DOI   ScienceOn
12 Rawal, N., Mollefors, K., Axelsson, K., Lingardh, G., and Widman B., An experimental study of urodynamic effects of epidural morphine and of naloxone reversal. Anesth. Analg., 62, 641-647 (1983)
13 Attali, B., Saya, D., Nah, S. Y., and Vogel, Z., Kappa opiate agonists inhibit $Ca^{2+}$ influx in rat spinal cord-dorsal root ganglion cocultures. Involvement of a GTP-binding protein. J. Biol. Chem., 264, 347-353 (1989)
14 Martin, W. R., Eades, C. G., Thompson, J. A., Huppler, R. E., and Gilbert, P. E., The effects of morphine- and nalorphinelike drugs in the nondependent and morphine-dependent chronic spinal dog. J. Pharmacol. Exp. Ther., 197, 517-532 (1976)
15 Bertalmio, A. J. and Woods, J. H., Discriminative stimulus effects of cyclorphane: selective antagonism with naltrexone. Psychopharmacology (Berl), 106, 189-194 (1992)   DOI
16 Dickenson, A. H., Neurotransmitters, Drugs and Disease, in Webster R. A. and Jordan C. C. (Ed), Blackwell Scientific Publications, Oxford, p265 (1989)
17 Oh, S., Kim, J. I., Chung, M. W., and Ho, I. K., Modulation of NMDA receptor subunit mRNA in butorphanol-tolerant and – withdrawing rats. Neurochem. Res., 25, 1603-1611 (2000)   DOI   ScienceOn
18 Suzuki, T. and Misawa, M., Physical dependence on morphine using the mu receptor deficient CXBK mouse. Prog. Clin. Biol. Res., 328, 519-522 (1990)
19 Walker, E. A. and Young, A. M., Discriminative-stimulus effects of the low efficacy ${\mu}$agonist nalbuphine. J. Pharmacol Exp. Ther., 267, 322-330 (1993)
20 Laurie, D. J. and Seeburg, P. H., Ligand affinities at recombination N-methyl-D-aspartate receptors depend on subunit composition. Eur. J. Pharmacol. Mol. Pharmacol. Sect., 268, 335-345 (1994)   DOI   ScienceOn
21 Kumor, K. M., Haertzen, C. A., Johnson, R. E., Kocher, T., and Jasinsi, D., Human psychopharmacology of ketocyclazocine as compared with cyclazocine, morphine and placebo. J. Pharmacol. Exp. Ther., 238, 960-968 (1986)
22 Di Chiara, G. and Imperato, A., Oposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumbens and in the dorsal caudate of freely moving rats. J. Pharmacol. Exp. Ther., 244, 1076-1080 (1988)
23 Gringauz, M., Rabinowitz, R., Stav, A., and Korczyn, A. D., Tolerance to the analgesic effect of buprenorphine, butorphanol, nalbuphine, and cyclorphan, and cross-tolerance to morphine. J. Anesth., 15, 204-209 (2001)   DOI
24 Zhu, H. and Ho, I. K., NMDA-R1 antisense attenuates morphine withdrawal behaviors. Eur. J. Pharmacol., 352, 151-156 (1998)   DOI   ScienceOn
25 Aceto, M. D., Dewey, W. L., Portoghese, P. S., and Takemori, A. E., Effects of beta-funaltrexamine (beta-FNA) on morphine dependence in rats and monkeys. Eur. J. Pharmacol., 123, 387-393 (1986)   DOI   ScienceOn
26 Cherubini, E. and North, R. A., Mu and kappa opioids inhibit transmitter release by different mechanisms. Proc. Natl. Acad. Sci. U.S.A., 82, 1860-1863 (1985)
27 Fukagawa, Y., Katz, J. L., and Suzuki, T., Effects of a selective kappa-opioid agonist, U-50,488H, on morphine dependence in rats. Eur. J. Pharmacol., 170, 47-51 (1989)   DOI   ScienceOn
28 Werz, M. A. and MacDonald, R. L., Dynorphin and neoendorphin peptides decrease dorsal root ganglion neuron calciumdependent action potential duration. J. Pharmacol. Exp. Ther., 234, 49-56 (1985)
29 Millan, M. J., Kappa-opioid receptors and analgesia. Trends Pharmacol. Sci., 11, 70-76 (1990)   DOI   ScienceOn
30 Shippenberg, T. S., Emmett-Oglesby, N. W., Ayesta, F. J., and Herz, A., Tolerance and selective cross-tolerance to the motivational effects of opioids. Psychopharmacology, 96, 110-115 (1988)   DOI
31 Spanagel, R., Herz, A., and Shippenberg, T. S., Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc. Natl. Acad. Sci. U.S.A., 89, 2046-2050 (1992)
32 Lord, J. A. H., Waterfield, A. A., Hughes, J., and Kostrlitz, H. W., Endogenous opioid peptides: multiple agonists and receptors. Nature, 267, 495-499 (1977)   DOI   ScienceOn
33 Sakurai, S. Y., Penny, J. B., and Young, A. B., Regionally distinct N-methyl-D-aspartate receptors distinguished by quantitative autoradiography of [$^{3}H$]MK-801 binding in rat brain. J. Neurochem., 60, 1344-1353 (1993)   DOI
34 Suzuki, T., Funada, M., Narit, M., Misawa M., and Nagase H., Pertussis toxin abolishes mu- and delta-opioid agonistinduced place preference. Eur. J. Pharmacol., 205, 85-88 (1991)   DOI   ScienceOn
35 Huidobro-Taro, J. P. and Parada, S., Kappa-opiates and urination: pharmacological evidence for an endogenous role of the kappa-opiate receptor in fluid and electrolyte balance. Eur. J. Pharmacol., 107, 1-10 (1984)   DOI   ScienceOn
36 Penning, J. P., Samson, B., and Baxter, A. D., Reversal of epidural morphine-induced respiratory depression and pruritus with nalbuphine. Can. J. Anaesth., 35, 599-604 (1988)   DOI
37 Suzuki, T., Fukagawa, Y., Yoshii, T., and Yanaura, S., Effect of opioid agonist-antagonist interaction on morphine dependence in rats. Life Sci., 42, 2729-2737 (1988)   DOI   ScienceOn
38 Rothman, R. B., Long, J. B., Bykov, V., Jacobson, A. E., Rice, K. C., and Holaday J. W., ${\beta}$-FNA binds irreversibly to the opiate receptor complex: in vivo and in vitro evidence. J. Pharmacol. Exp. Ther., 247, 405-416 (1988)
39 Pfeiffer, A., Brantl, V., Herz, A., and Emrich, H. M., Psychotomimesis mediated by kappa opiate receptors. Science, 233, 774-776 (1986)   DOI
40 Pick, C. G., Paul, D., and Pastemak, G. W., Nalbuphine, a mixed kappa 1 and kappa 3 analgesic in mice. J. Pharmacol. Exp. Ther., 262, 1044-1050 (1992)