Skip to main content
SpringerLink
Log in

Modulation of NMDA Receptor Subunit mRNA in Butorphanol-Tolerant and —Withdrawing Rats

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

The NMDA receptor has been implicated in opioid tolerance and withdrawal. The effects of continuous infusion of butorphanol on the modulation of NMDA receptor subunit NR1, NR2A, NR2B, and NR2C gene expression were investigated by using in situ hybridization technique. Continuous intracerebroventricular (i.c.v.) infusion with butorphanol (26 nmol/μl/h) resulted in significant modulations in the NR1, NR2A, and NR2B mRNA levels. The level of NR1 mRNA was significantly decreased in the cerebral cortex, thalamus, and CA1 area of hippocampus in butorphanol tolerant and withdrawal (7 h after stopping the infusion) rats. The NR2A mRNA was significantly decreased in the CA1 and CA3 of hippocampus in tolerant rats and increased in the cerebral cortex and dentate gyrus in butorphanol withdrawal rats. NR2B subunit mRNA was decreased in the cerebral cortex, caudate putamen, thalamus, CA3 of hippocampus in butorphanol withdrawal rats. No changes of NR1, NR2A, NR2C subunit mRNA in the cerebellar granule cell layer were observed in either butorphanol tolerant or withdrawal rats. Using quantitative ligand autoradiography, the binding of NMDA receptor ligand [3H]MK-801 was increased significantly in all brain regions except in the thalamus and hippocampus, at the 7 hr after stopping the butorphanol infusion. These results suggest that region-specific changes of NMDA receptor subunit mRNA (NR 1 and NR2) as well as NMDA receptor binding ([3H]MK-801) are involved in the development of tolerance to and withdrawal from butorphanol.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Hoover, R. C. and Williams, R. B. 1985. Survey of butorphanol and nalbuphine diversion in U.S. hospitals. Am. J. Hosp. Pharm. 42:1111–1113.

    Google Scholar 

  2. Smith, S. G. and Davis, W. M. 1984. Nonmedical use of butorphanol and diphenylhydramine. J. Am. Med. Assoc. 252:1010.

    Google Scholar 

  3. Evans, W. S., Bowen, J. N., Giordano, F., and Clark, B. 1985. A case of stadol dependence. J. Am. Med. Assoc. 253:2191–2192.

    Google Scholar 

  4. Brown, G. R. 1985. Stadol dependence: another case. J. Am. Med. Assoc. 254:910.

    Google Scholar 

  5. Chang, K. J., Wei, E. T., Killian, A., and Chang, J. K. 1983. Potent morphiceptin analogs: structure activity relationships and morphine-like activities. J. Pharmacol. Exp. Ther. 227:403–408.

    Google Scholar 

  6. Lahti, R. A., Mickelson, M. M., McCall, J. M., and Von Voightlander, P. F. 1985. [3H]U-69,593: a highly selective ligand for the opioid κ receptor. Eur. J. Pharmacol. 109:281–284.

    Google Scholar 

  7. Jaw, S. P., Hoskins, B., and Ho, I. K. 1993. Opioid antagonists and butorphanol dependence. Pharmacol. Biochem. Behav. 44:497–500.

    Google Scholar 

  8. Jaw, S. R., Hoskins, B., and Ho, I. K. 1993. Involvement of δ-opioid receptors in physical dependence on butorphanol. Eur. J. Pharmacol. 240:67–72.

    Google Scholar 

  9. Jaw, S. P., Makimura, M., Hoskins, B., and Ho, I. K. 1993. Effect of norbinaltorphimine on butorphanol dependence. Eur. J. Pharmacol. 239:133–140.

    Google Scholar 

  10. Coutinho-Netto, J., Abdul-Ghani, A., and Bradford, H. F. 1980. Suppression of evoked and spontaneous release of neurotransmitters in vivo by morphine. Biochem. Pharmacol. 29:2777–2780.

    Google Scholar 

  11. Crowder, J. M., Norris, D. K., and Bradford, H. F. 1986. Morphine inhibition of calcium fluxes, neurotransmitter release and protein and lipid phosphorylation in brain slices and synaptosomes. Biochem. Pharmacol. 35:2501–2507.

    Google Scholar 

  12. Gannon, R. L. and Tertian, D. M. 1991. U-50,488H inhibits dynorphine and glutamate release from guinea pig hippocampal mossy fiber terminals. Brain Res. 548:242–247.

    Google Scholar 

  13. Nicol, B., Rowotham, D. J., and Lambert, D. G. 1996. μ-and κ-Opioids inhibit K+evoked glutamate release from rat cerebrocortical slices. Neurosci. Lett. 218:79–82.

    Google Scholar 

  14. Aghajanian, G. K., Kogan, J. H., and Moghaddam, B. 1994. Opiate withdrawal increases glutamate and aspartate efflux in the locus coeruleus: an in vivo microdialysis study. Brain Res. 636:126–130.

    Google Scholar 

  15. Zhang, T., Feng, Y. Z., Rockhold, R. W., and Ho, I. K. 1994. Naloxone-precipitated morphine withdrawal increases pontine glutamate levels in the rat. Life Sci. 55:PL25–PL31.

    Google Scholar 

  16. Feng, Y. Z., Zhang, T., Rockhold, R. W., and Ho, I. K. 1995. Increased locus coeruleus glutamate levels are associated with naloxone-precipitated withdrawal from butorphanol in the rat. Neurochem. Res. 20:745–751.

    Google Scholar 

  17. Taylor, C. P., Geer, J. J., and Burke, S. P. 1992. Endogenous extracellular glutamate accumulation in rat neocortical cultures by reversal of the transmembrane sodium gradient. Neurosci. Lett. 145:197–200.

    Google Scholar 

  18. Koyuncuoglu, H., Gungor, M., Sagduyu, H., and Aricioglu, F. 1990. Suppression by ketamine and dextromethorphan of precipitated abstinence syndrome in rats. Pharmacol. Biochem. Behav. 35:829–832.

    Google Scholar 

  19. Rasmusssen, K., Fuller, R. W., Stockton, M. E., Perry, K. W., Swinford, R. M., and Ornstein, P. L. 1991. NMDA receptor antagonists suppress behaviors but not norepinephrine turnover or locus coeruleus unit activity induced by opiate withdrawal. Eur. J. Pharmacol. 117:9–16.

    Google Scholar 

  20. Koyuncuoglu, H., Dizdar, Y., Aricioglu, F., and Sayin, U. 1992. Effects of MK-801 on morphine physical dependence: attenuation and intensification. Pharmacol. Biochem. Behav. 43:487–490.

    Google Scholar 

  21. Tokuyama, S., Wakabayashi, H., and Ho, I. K. 1996. Direct evidence for a role of glutamate in the expression of opioid withdrawal syndrome. Eur. J. Pharmacol. 295:123–129.

    Google Scholar 

  22. Zhu, H. and Ho, I. K. 1998. NMDA-R1 antisense attenuates morphine withdrawal behaviors. Eur. J. Pharmacol. 352: 151–156.

    Google Scholar 

  23. Monyer, H., Sprengel, R., Schoepfer, R., Herb, A., Higuchi, M., Lomeli, H., Burnashev, N., Sakmenn, B., and Seeberg, P. H. 1992. Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science 256:1217–1221.

    Google Scholar 

  24. Paxinos, G. and Watson, C. 1986. The rat brain in storeotaxic coordinates, 2nd edit., Academic Press, Orland, Florida.

    Google Scholar 

  25. Horan, P. and Ho, I. K. 1991. The physical dependence liability of butorphanol: a comparative study with morphine. Eur. J. Pharmacol. 203:387–391.

    Google Scholar 

  26. Sakurai, S. Y., Penny, J. B., and Young, A. B. 1993. Regionally distinct N-methyl-D-aspartate receptors distinguished by quantitative autoradiography of [3H]MK-801 binding in rat brain. J. Neurochem. 60:1344–1353.

    Google Scholar 

  27. Moriyoshi, K., Masu, M., Ishii, T., Shigemoto, R., Mizuno, N., and Nakanishi, S. 1991. Molecular cloning and characterization of the rat NMDA receptor. Nature 354:31–37.

    Google Scholar 

  28. Ishii, T., Moriyoshi, K., Sugihara, H., Sakurada, K., Kadotani, H., Yokoi, M., Akazawa, C., Shigemoto, R., Mizuno, N., Masu, M., and Nakanishi, S. 1993. Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits. J. Biol. Chem. 268:2836–2843.

    Google Scholar 

  29. Laurie, D. J. and Seeburg, P. H. 1994. Ligand affinities at recombinant N-methyl-D-aspartate receptors depend on subunit composition. Eur. J. Pharmacol. Mol. Pharmacol. Sect. 268: 335–345.

    Google Scholar 

  30. Zhu, H., Jang, C. G., Ma, T., Oh, S., Rockhold, R. W., and Ho, I. K. 1999. Region specific expression of NMDA receptor NR1 subunit mRNA in hypothalamus and pons following chronic morphine treatment. Eur. J. Pharmacol. 365:47–54.

    Google Scholar 

  31. Wenzel, A., Fritschy, J. M., Mohler, H., and Benke, D. 1997. NMDA receptor heterogeneity during postnatal development of the rat brain: differential expression of the NR2A, NR2B, and NR2C subunit proteins. J. Neurochem. 68:469–478.

    Google Scholar 

  32. Resink, A., Villa, M., Benke, D., Mohler, H., and Balazs, R. 1995. Regulation of the expression of NMDA receptor subunit in rat cerebellar granule cells: effect of chronic K+-induced depolarization and NMDA exposure. J. Neurochem. 64:558–565.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuroscience and Medical Research Center, College of Medicine, Ewha Womans University, Mokdong, Yangchon-ku, Seoul, 158-710, Korea

    Seikwan Oh

  2. Division of General Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul, 122-704, Korea

    Joo-Il Kim & Myeon-Woo Chung

  3. Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, 39216

    Ing K. Ho

Authors
  1. Seikwan Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joo-Il Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Myeon-Woo Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ing K. Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oh, S., Kim, JI., Chung, MW. et al. Modulation of NMDA Receptor Subunit mRNA in Butorphanol-Tolerant and —Withdrawing Rats. Neurochem Res 25, 1603–1611 (2000). https://doi.org/10.1023/A:1026618603795

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026618603795

Search

Navigation