Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Parkinsonian-like locomotor impairment in mice lacking dopamine D2 receptors

Abstract

DOPAMINERGIC neuronal pathways arise from mesencephalic nuclei and project axons to the striatum, cortex, limbic system and hypothalamus1,2. Through these pathways dopamine affects many physiological functions, such as the control of coordinated movement and hormone secretion3. Here we have studied the physiological involvement of the dopamine D2 receptors in dopaminergic transmission, using homologous recombination to generate D2-receptor-deficient mice. Absence of D2 receptors leads to animals that are akinetic and bradykinetic in behavioural tests, and which show significantly reduced spontaneous movements. This pheno-type presents analogies with symptoms characteristic of Parkin-son's disease4,5. Our study shows that D2 receptors have a key role in the dopaminergic control of nervous function. These mice have therapeutic potential as a model for investigating and correcting dysfunctions of the dopaminergic system.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Purchase on Springer Link

Instant access to full article PDF

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Graybiel, A. M., Trends Neurosci. 13, 244–254 (1990).

    Article  CAS  Google Scholar 

  2. Alexander, G. A. & Crutcher, M. D. Trends Neurosci. 13, 266–271 (1990).

    Article  CAS  Google Scholar 

  3. Jackson, D. M. & Westlind-Danielsson, A. Pharmac. Ther. 64, 291–369 (1994).

    Article  CAS  Google Scholar 

  4. Hornykiewicz, O. Pharmac. Rev. 18, 925–964 (1966).

    CAS  Google Scholar 

  5. Seeman, P. & Niznik, H. B. FASEB J. 4, 2737–2744 (1990).

    Article  CAS  Google Scholar 

  6. Adra, C. N., Boer, P. H. & McBurney, M. W. Gene 60, 65–74 (1987).

    Article  CAS  Google Scholar 

  7. Lévesque, D. et al. Proc. natn. Acad. Sci. U.S.A. 89, 8155–8159 (1992).

    Article  ADS  Google Scholar 

  8. Zurawski, G. et al. Science 232, 772–775 (1986).

    Article  ADS  CAS  Google Scholar 

  9. Bannon, M. J. et al. J. biol. Chem. 261, 6640–6642 (1986).

    CAS  PubMed  Google Scholar 

  10. Civelli, O., Douglass, J., Goldstein, A. & Herbert, E. Proc. natn. Acad. Sci. U.S.A. 82, 4291–4295 (1985).

    Article  ADS  CAS  Google Scholar 

  11. Kaufman, D. L., McGinnis, J. F., Krieger, N. R. & Tobin, A. J. Science 232, 1138–1140 (1986).

    Article  ADS  CAS  Google Scholar 

  12. Grima, B., Lamouroux, A., Blanot, F., Biguet, N. F. & Mallet, J. Proc. natn. Acad. Sci. U.S.A. 82, 617–621 (1985).

    Article  ADS  CAS  Google Scholar 

  13. Le Moine, C., Normand, E. & Bloch, B. Proc. natn. Acad. Sci. U.S.A. 88, 4205–4209 (1991).

    Article  ADS  CAS  Google Scholar 

  14. Kita, H. & Kitai, S. T. Brain Res. 447, 346–352 (1988).

    Article  CAS  Google Scholar 

  15. Gerfen, C. R. et al. Science 250, 1429–1432 (1990).

    Article  ADS  CAS  Google Scholar 

  16. Fuxe, K., Hökfelt, T. & Nilsson, O. Neuroendocrinology 5, 5–15 (1987).

    Google Scholar 

  17. Janssen, P. A. J., Jageneau, A. H. & Schellekens, K. H. L. Psychopharmacologia 1, 389–392 (1960).

    Article  CAS  Google Scholar 

  18. Pertwee, R. G. Br. J. Pharmac. 46, 753–763 (1972).

    Article  CAS  Google Scholar 

  19. Wolffgramm, J., Rommelspacher, H. & Buck, E. Pharmac. Biochem. Behav. 36, 907–914 (1990).

    Article  CAS  Google Scholar 

  20. Xu, M. et al. Cell 79, 729–742 (1994).

    Article  CAS  Google Scholar 

  21. Gingrich, J. A. & Caron, M. G. A. Rev. Neurosci. 16, 299–321 (1993).

    Article  CAS  Google Scholar 

  22. Drago, J. et al. Proc. natn. Acad. Sci. U.S.A. 91, 12564–12568 (1994).

    Article  ADS  CAS  Google Scholar 

  23. Meyer, M. E., Cottrell, G. A. & Van Hartesveldt, C. Pharmac. Biochem. Behav. 41, 507–510 (1992).

    Article  CAS  Google Scholar 

  24. Morelli, M. & Di Chiara Eur. J. Pharmac. 117, 179–185 (1985).

    Article  CAS  Google Scholar 

  25. Ögren, S. O. & Fuxe, K. Neurosci. Lett. 85, 333–338 (1988).

    Article  Google Scholar 

  26. Casey, D. E. Psychopharmacology, 107, 18–22 (1992).

    Article  CAS  Google Scholar 

  27. Montmayeur, J.-P. et al. FEBS Lett 278, 239–243 (1991).

    Article  CAS  Google Scholar 

  28. Montmayeur, J.-P., Guiramand, J. & Borrelli, E. Molec. Endocr. 7, 161–170 (1993).

    CAS  PubMed  Google Scholar 

  29. Guiramand, J., Montmayeux, J. P., Ceraline, J., Bhatia, M. & Borrelli, E. J. biol. Chem. 270, 7354–7358 (1995).

    Article  CAS  Google Scholar 

  30. Dollé, P., Ruberte, E., Leroy, P., Moucis-Kay, G. & Chambon, P. Development 110, 1133–1151 (1990).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baik, JH., Picetti, R., Saiardi, A. et al. Parkinsonian-like locomotor impairment in mice lacking dopamine D2 receptors. Nature 377, 424–428 (1995). https://doi.org/10.1038/377424a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/377424a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing