Advertisement

Reduction of Dopamine Receptor Activity Differentially Alters Striatal Neuropeptide mRNA Levels

  • Jesus A. Angulo
  • Greg R. Christoph
  • Robert W. Manning
  • Beth A. Burkhart
  • Leonard G. Davis
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 221)

Summary

We have investigated the effect of dopamine receptor blockade on striatal proenkephalin mRNA and protachykinin mRNA by Northern gel analysis and by in situ hybridization histochemistry. Chronic haloperidol treatment resulted in a 3.5 fold increase in striatal proenkephalin mRNA and a 30% decrease in protachykinin mRNA (no apparent change in α-tubulin mRNA was observed). The changes in mRNA levels for protachykinin and proenkephalin were uniform throughout the caudate-putamen of the rat as determined by in situ hybridization histochemistry. The results imply that altering receptor-mediated neurotransmitter functions can lead to profound, specific, and long-lasting alterations in neuronal gene expression.

Keywords

Osmotic Minipumps Haloperidol Treatment Hybridization Histochemistry Guanidine Isothiocyanate Neuronal Gene Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Angulo, J. A., Davis, L. G., Burkhart, B. A. and Christoph, G. R., Reduction of striatal dopaminergic neurotransmission elevates striatal proenkephalin mRNA, Eur. J. Pharm. 130: 341–343 (1986).CrossRefGoogle Scholar
  2. Angulo, J. A., Manning, R. W., Davis, L. G., Burkhart, B. A. and Christoph, G. R., In situ hybridization of substance P mRNA in rat brain using synthetic oligonucleotide probes based on the nucleotide sequence of the rat substance P mRNA, Soc. Neurosci. 12 (Abst. #379.6): 1397 (1986).Google Scholar
  3. Bannon, M. J., Lee, J.-M., Giraud, P., Young, A., Affolter, H.-U. and Bonner, T. I., Dopamine antagonist haloperidol decreases substance P, substance K, and preprotachykinin mRNAs in rat striatonigral neurons, J. Biol. Chem. 261: 6640–6644 (1986).Google Scholar
  4. Bloch, B., Popovici, T., Le Guellec, D., Normand, E., Chouham, S., Guitteny, A. F. and Bohlen, P., In situ hybridization histochemistry for the analysis of gene expression in the endocrine and central nervous system tissues: A 3-year experience, J. Neurosci. Res. 16: 183–200 (1986).CrossRefGoogle Scholar
  5. Davis, L. G., Dibner, M. D. and Battey, J. F., Basic Methods in Molecular Biology, Elsevier (New York) (1986).Google Scholar
  6. Ehrlich, Y. H., Phosphoproteins as specifiers for mediators and modulators of neural function. In: Modulators, Mediators, and Specifiers in Brain Function edited by Y. H. Ehrlich, J. Volavka, L. G. Davis, and E. G. Brunngraber (Plenum, New York), Adv. Exp. Med. and Biol. 116: 75–101 (1979).Google Scholar
  7. Hong, J. S., Yong, H. Y. and Costa, E., Substance P content of substantia nigra after chronic treatment with antischizophrenic drugs, Neuropharmacol. 17: 83–85 (1978).CrossRefGoogle Scholar
  8. Howells, R. D., Kilpatrick, D. L., Bhatt, R., Monahan, J. J., Poonian, M. and Udenfriend, S., Molecular cloning and sequence determination of rat preproenkephalin cDNA: Sensitive probe for studying transcriptional changes in rat tissue, Proc. Natl. Acad. Sci. USA 81: 7651–7655 (1984).CrossRefGoogle Scholar
  9. Jessell, T. M., Emson, P. C., Paxinos, G. and Cuello, A. C., Topographic projections of substance P and GABA pathways in the striato-and pallidonigral system, Br. Res. 152: 487–498 (1978).CrossRefGoogle Scholar
  10. Kebabian, J. W. and Calne, D. B., Multiple receptors for dopamine, Nature 277: 93–96 (1979).CrossRefGoogle Scholar
  11. Kubota, Y., Inagaki, S., Kito, S., Takagi, H. and Smith, A. D., Ultrastructural evidence of dopaminergic input to enkephalinergic neurons in rat neostriatum, Br. Res. 367: 374–378 (1986).CrossRefGoogle Scholar
  12. Lemischka, I. P., Farmer, S., Racaniello, V. R. and Sharp, P. A., Nucleotide sequence and evolution of a mammalian alpha-tubulin messenger RNA, J. Mol. Biol. 151: 101–120 (1981).CrossRefGoogle Scholar
  13. Nawa, H., Hirose, T., Takashima, H., Inayama, S. and Nakanishi, S., Nucleotide sequences of cloned cDNAs for two types of bovine brain substance P precursor, Nature 306: 32–36 (1983).CrossRefGoogle Scholar
  14. Sabol, S. L., Yoshikawa, K. and Hong, J.-S., Regulation of methionine-enkephalin precursor messenger RNA in rat striatum by haloperidol and lithium, Biochem. Biophys. Res. Comm. 113: 391–399 (1983).CrossRefGoogle Scholar
  15. Sanger, F., Nicklen, S. and Coulson, A. R., DNA sequencing with chain-terminating inhibitors, Proc. Natl. Acad. Sci. USA 75: 5463–5467 (1977).CrossRefGoogle Scholar
  16. Shivers, B. D., Harlan, R. E., Romano, G. J., Howells, R. D. and Pfaff, D. W., Cellular localization of proenkephalin mRNA in rat brain: Gene expression in the caudate-putamen and cerebellar cortex, Proc. Natl. Acad. Sci. USA 83: 6221–6225 (1986).CrossRefGoogle Scholar
  17. Siggins, G. R., Hoffer, B. J., Bloom, F. E. and Ungerstedt, U., Cytochemical and Electrophysiological studies of dopamine in the caudate nucleus, in: The Basal Ganglia edited by M. D. Yahr, Raven Press, NY 227–248 (1976).Google Scholar
  18. Tang, F., Costa, E. and Schwartz, J. P., Increase of proenkephalin mRNA and enkephalin content of rat striatum after daily injection of haloperidol for 2 to 3 weeks, Proc. Natl. Acad. Sci. USA 80: 3841–3844 (1983).CrossRefGoogle Scholar
  19. Young, W. S. III, Bonner, T. I., Brann, M. R., Mesencephalic dopamine neurons regulate the expression of neuropeptide mRNAs in the rat forebrain, Proc. Natl. Acad. Sci. USA 83: 9827–9831 (1986).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Jesus A. Angulo
    • 1
  • Greg R. Christoph
    • 1
  • Robert W. Manning
    • 1
  • Beth A. Burkhart
    • 1
  • Leonard G. Davis
    • 1
  1. 1.Medical Products DepartmentNeurobiology Group, E. I. du Pont de Nemours and Co.WilmingtonUSA

Personalised recommendations