Skip to main content
SpringerLink
Log in

Mu opioid receptor mRNA in nucleus accumbens is elevated following dopamine receptor activation

  • Reward/Drug Abuse Mechanisms
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

We have previously demonstrated that continuous cocaine treatment for three days induces a marked but transient increase in mu opioid receptor (MOR) mRNA in nucleus accumbens (n. acc.); SCH 23390 and eticlopride, selective antagonists of D1- and D2-like dopamine (DA) receptors, respectively, blocked this cocaine-induced upregulation of MOR mRNA in n. acc. suggesting involvement of both subfamilies of DA receptors in the effect of cocaine (1,2). In the present study the ability of the selective DA D3 receptor antagonist, nafadotride (3,4), to prevent the cocaine-induced upregulation of MOR mRNA in n. acc. has been examined. Also, regulation of MOR mRNA following chronic administration of the DA agonists, SKF 38393, R(+)-6-Bromo-APB hydrobromide, or bromocriptine, has been studied. Male Sprague-Dawley rats were treated for 3 days with saline, cocaine, the DA receptor agonists or antagonistsdelivered by osmotic minipump. Expression of MOR mRNA in n. acc. was estimated by quantitative competitive polymerase chain reaction (PCR) assays following reverse transcription. Nafadotride (1.0 mg/kg/day) prevented the cocaine-induced upregulation of MOR mRNA in n. acc. When administered alone, nafadotride did not change the expression of MOR mRNA. The levels of MOR mRNA were elevated in n. acc. after 3 days treatment with each of the DA agonists, SKF 38393 (4.0 mg/kg/day), R(+)-6-Bromo-APB hydrobromide (4.0 mg/kg/day), or bromocriptine (5.0 mg/kg/day). Thus, DA agonists mimick the effect of cocaine on the expression of MOR mRNA in n. acc. These data confirm the involvement of dopaminergic mechanisms in the mediation of cocaine effects, indicate the comparability of actions of indirect and direct DA agonists, and point to the usefulness of cocaine as a tool to expose interaction between dopaminergic and opioid systems. The results suggest that activation of more than one type of DA receptor is required for the increased expression of MOR mRNA.

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

Abbreviations

DA:

dopamine

mRNA:

messenger ribonucleic acid

MOR:

mu opioid receptor

n. acc.:

nucleus accumbens

PCR:

polymerase chain reaction

R(+)-6-Bromo-APB hydrobromide:

R(+)-6-Bromo-7,8-dihydroxy-3-allyl-l-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide

References

  1. Azaryan, A. V., Coughlin, L. J., Búzás, B., Clock, B. J., and Cox, B. M. 1996. Effect of chronic cocaine treatment on μ- and δ-opioid receptor mRNA levels in dopaminergically innervated brain regions. J. Neurochem. 66:443–448.

    Article  PubMed  CAS  Google Scholar 

  2. Azaryan, A. V., Clock, B. J., and Cox, B. M. 1996. Transient upregulation of mu opioid receptor mRNA in nucleus accumbens during chronic cocaine administration. FASEB J. 10: p. A448.

    Google Scholar 

  3. Griffon, N., Diaz, J., Levesque, D., Sautel, F., Schwartz, J.-C., Sokoloff, P., Simon, P., Costentin, J., Garrido, F., Mann A., and Wermuth, C. 1995. Localization, regulation and role of the dopamine D3 receptor are distinct from those of the D2 receptor. Clinical Neuropharmac. 18:S130-S142.

    Article  Google Scholar 

  4. Sokoloff, P. and Schwartz, J.-C. 1995. Novel dopamine receptors: half a decade later. Trends Pharm. Sci. 16:270–275.

    Article  PubMed  CAS  Google Scholar 

  5. Ritz, M. C., Lamb, R. Y., Goldberg, S. R., and Kuhar, M. J. 1987. Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science 237:1219–1223.

    Article  PubMed  CAS  Google Scholar 

  6. Kuhar, M. J., Ritz M. C., and Boja, J. W. 1991. The dopamine hypothesis of reinforcing properties of cocaine. Trends Neuroscience 14:299–302.

    Article  CAS  Google Scholar 

  7. Unterwald, E. M., Ho, A., Rubenfeld, J. M., and Kreek, M. J. 1994a. Time course of the development of behavioral sensitization and dopamine receptor upregulation during binge cocaine administration. J. Pharm. Exp. Therap. 270:1387–1397.

    CAS  Google Scholar 

  8. Meador-Woodruff, J. H., Little, K. Y., Damask, S. P., and Watson, S. J. 1995. Effects of cocaine on D3 and D4 receptor in rat striatum. Biol. Psychiatry 38:263–266.

    Article  PubMed  CAS  Google Scholar 

  9. Sivam, S. P. 1989. Cocaine selectively increases striatonigral dynorphin levels by a dopaminergic mechanism. J. Pharm. Exp. Therap. 250:818–824.

    CAS  Google Scholar 

  10. Smiley, P. L., Johnson, M., Bush, L., Gibb, J. W., and Hanson, G. R. 1990. Effects of cocaine on extrapyramidal and limbic dynorphin systems. J. Pharm. Exper. Therap. 253:938–943.

    CAS  Google Scholar 

  11. Hurd, Y. L., Brown, E. E., Finlay, J. M., Fibiger, H. C., and Gerfen, C. R. 1992. Cocaine self-administration differentially alters mRNA expression of striatal peptides. Molec. Brain Res. 13: 165–170.

    Article  PubMed  CAS  Google Scholar 

  12. Spangler, R., Unterwald, E. M., and Kreek, M. J. 1993. ‘Binge’ cocaine administration induces a sustained increase of prodynorphin mRNA in rat caudate-putamen. Mol. Brain Res. 19: 323–327.

    Article  PubMed  CAS  Google Scholar 

  13. Romualdi, P., Donatini, A., Izenwasser, S., Cox, B. M., and Ferri, S. 1996. Chronic intracerebroventricular cocaine differentially affects prodynorphin gene expression in rat hypothalamus and caudate-putamen. Mol. Brain Res., in press.

  14. Hammer, Jr. P. P. 1989. Cocaine alters opiate receptor binding in critical brain reward regions. Synapse 3:55–60.

    Article  PubMed  CAS  Google Scholar 

  15. Ishizuka, Y., Rockhold, R. W., Hoskins, B., and Ho, I. K. 1988. Cocaine-induced changes in3H-naloxone binding in brain membranes isolated from spontaneously hypertensive and Wistar-Kyoto rats. Life Sci. 43:2275–2282.

    Article  PubMed  CAS  Google Scholar 

  16. Unterwald, E. M., Rubenfeld, J. M., and Kreek, M. J. 1994b. Repeated cocaine administration upregulates κ and μ, but not δ, opioid receptors. NeuroReport 5:1613–1616.

    Article  PubMed  CAS  Google Scholar 

  17. Chromczynsky, P. and Sacchi, N. 1987. Single step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162:156–159.

    Article  Google Scholar 

  18. Siebert, P. D. and Larrick, J. W. 1992. Competitive PCR. Nature 359:557–558.

    Article  PubMed  CAS  Google Scholar 

  19. Búzás, B., and Cox, B. M. 1994. Competitive PCR assay for quantitation of mu and delta opioid receptor messenger-RNA levels in small tissue samples. Regulatory Peptides 54:35–36.

    Article  Google Scholar 

  20. Búzás, B., and Cox, B. M. 1996. Quantitative analysis of mu and delta opioid receptor gene expression in rat brain and peripheral ganglia using competitive polymerase chain reaction. Neurosci., in press.

  21. Zahm, D. S., and Brog, J. S. 1992. Commentary: On the significance of subterritories in the accumbens part of the ventral striatum. Neuroscience 50:751–767.

    Article  PubMed  CAS  Google Scholar 

  22. Koob, G. F., and Goeders, N. E. 1988. Neuroanatomical substrates of drug self-administration. Pages 214–263, Liebman, J. M., and Cooper, S. J. (ed)in Neuropharmacological Basis of Reward. Oxford University Press, New York.

    Google Scholar 

  23. Koob, G. F. 1992. Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Neurosci. 13:177–184.

    CAS  Google Scholar 

  24. Wise, R. A., and Bozarth, M. A. 1987. A psychomotor stimulant theory of addiction. Psychol. Rev. 94:469–492.

    Article  PubMed  CAS  Google Scholar 

  25. Cooper, S. J. 1991. Interactions between endogenous opioids and dopamine: Implications for reward and aversion. Pages 331–366,in The Mesolimbic Dopamine System: From Motivation to Action. John Wiley and Sons, Ltd. London.

    Google Scholar 

  26. Meador-Woodruff, J. H., Grandy, D. K., Van Tol, H. H. M., Damask, B., Karley, S., Little, Y., Civelli, O., Watson, S. J. 1994. Dopamine receptor gene expression in the human medial temporal lobe. Neuropsychopharmacology 10:239–248.

    PubMed  CAS  Google Scholar 

  27. Curran, E. J., and Watson, S. J. 1995. Dopamine receptor mRNA expression patterns by opioid peptide cells in the nucleus accumbens of the rat: a double in situ hybridization study. J. Comp. Neurol. 361:57–76.

    Article  PubMed  CAS  Google Scholar 

  28. Chen, Y., Mestek, A., Liu, J., Hurley, J., and Yu, L. 1993. Molecular cloning and function expression of a μ-opioid receptor from rat brain. Mol. Pharmacol. 44:8–12.

    PubMed  CAS  Google Scholar 

  29. Mansour, A., Fox, C. A., Thompson, R. C., Akil, H., Watson, S. J. 1994. μ-Opioid receptor mRNA expression in the rat CNS: comparison to μ receptor binding. Brain Res. 643:245–265.

    Article  PubMed  CAS  Google Scholar 

  30. Mansour, A., Fox, C. A., Burke, S., Akil, H., and Watson, S. J. 1995. Immunohistochemical localization of the cloned mu opioid receptor in the rat CNS. J. Chem. Neuroanat. 8:283–305.

    Article  PubMed  CAS  Google Scholar 

  31. Arvidsson, U., Riedl, M., Chacrabarti, S., Lee, J.-H., Nakano, A. H., Dado, R. J., Loh, H. H., Law, P.-Y., Wessendorf, M. W., and Elde, R. 1995. Distribution and targeting of a mu-opioid receptor (MOR1) in brain and spinal cord. J. Neurosci. 15: 3328–3341.

    PubMed  CAS  Google Scholar 

  32. Self, D. W., and Stein, L. 1992. The D1 agonists SKF 89258 and SKF 77434 are self-administered by rats. Brain Res. 582: 349–352.

    Article  PubMed  CAS  Google Scholar 

  33. Self, D. W., Belluzzi, J. D., Kossuth, S., Stein, L. 1996. Self-administration of the D-1 agonist SKF 82958 is mediated by D-1, not by D-2, receptors. Psychopharmacol. 123:303–306.

    Article  CAS  Google Scholar 

  34. Rozenweig-Lipson, S., Hesterberg, P., Bergman, J. 1994. Observational studies of dopamine D1 and D2 agonists in squirrel monkeys. Psychopharmacol. 116:9–18.

    Article  Google Scholar 

  35. Britton, D. R., Curzon, P., Mackenzie, R. G., Kebabian, J. W., Williams, J. E., and Kerkman, D. 1991. Evidence for involvement of both D1 and D2 receptors in maintaining cocaine self-administration. Pharmac. Biochem. Behavior 39:911–915.

    Article  CAS  Google Scholar 

  36. Maldonado, R., Robledo, P., Chover, A. J., Caine, S. B., Koob, G. F. 1993. D1 dopamine receptors in the nucleus accumbens modulate cocaine self-administration in the rat. Pharmacol. Biochem. Behav. 45:239–242.

    Article  PubMed  CAS  Google Scholar 

  37. Hubner, C. B., and Koob, G. F. 1990. Bromocriptine produces decreases in cocaine self-administration in the rat. Neuropsychopharmacol. 3:101–108.

    CAS  Google Scholar 

  38. Callahan, P. M., and Cunningham, K. A. 1993. Discriminative stimulus properties of cocaine in relation to dopamine D2 receptor function in rats. J. Pharm. Exp. Therap. 266:585–592.

    CAS  Google Scholar 

  39. Lahti, R., Roberts, R., and Taminga, C. 1995. D2 family receptor distribution in human postmorten tissue: an autoradiographic study. NeuroReport 6:2505–2512.

    Article  PubMed  CAS  Google Scholar 

  40. Shetreat M., Lil, L., Wong, A., and Rayport, S. 1996. Visualization of D1 dopamine receptors on living nucleus accumbens neurons and their colocalization with D2 receptors. J. Neurochem. 66: 1475–1482.

    Article  PubMed  CAS  Google Scholar 

  41. Bouthenet, M. L., Souil, E., Martres, M. P., Sokoloff, P., Giros, B., Schwartz J. C. 1991. Localization of dopamine D3 receptor mRNA in the rat brain using in situ hybridization histochemistry: comparison with dopamine D2 receptor mRNA. Brain Res. 564: 203–219.

    Article  PubMed  CAS  Google Scholar 

  42. Landwehrmeyer, B., Mengod, G., Palacios, J. M. 1993. Differential visualization of dopamine D2 and D3 receptor sites in rat brain: a comparative study using in situ hybridization histochemistry and ligand binding autoradiography. Eur. J. Neurosci. 5: 145–153.

    Article  PubMed  CAS  Google Scholar 

  43. Diaz, J., Levesque, D., Lammers, C. H., Griffon, N., Martres, M.-P., Schwartz, J.-C., Sokoloff, P. 1995. Phenotypical characterization of neurons expressing the dopamine D3 receptor in the rat brain. Neurosci. 65:731–745.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., 20814, Bethesda, MD

    Anahit V. Azaryan, Barbara J. Clock & Brain M. Cox

Authors
  1. Anahit V. Azaryan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Barbara J. Clock
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brain M. Cox
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Special issue dedicated to Dr. Eric. J. Simon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Azaryan, A.V., Clock, B.J. & Cox, B.M. Mu opioid receptor mRNA in nucleus accumbens is elevated following dopamine receptor activation. Neurochem Res 21, 1411–1415 (1996). https://doi.org/10.1007/BF02532382

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02532382

Key words

Search

Navigation