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:

Direct hyperpolarizing action of baclofen on hippocampal pyramidal cells

Nature volume 308, pages 450–452 (1984)Cite this article

Abstract

Baclofen has been used as an antispastic agent for over a decade1, yet its mechanism of action is still not fully understood. While early iontophoretic studies revealed a depression of neuronal activity2–4, more recent studies have emphasized a presynaptic depression of transmitter release, both in the peripheral5,6 and central nervous sytem7–14, possibly resulting from a blockade of calcium channels15. Although baclofen is structurally similar to the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), none of its actions seem to be antagonized by the GABA antagonist, bicuculline. However, recent experiments have indicated that baclofen binds to a class of bicuculline-resistant GABA receptors, termed GABAB receptors16. Here, we have analysed the action of baclofen on the membrane potential of CA1 hippocampal pyramidal cells in vitro and report that it directly hyperpolarizes these cells in a potent, stereoselective manner which is resistant to bicuculline methiodide. This response is associated with a decrease in neuronal input resistance and may involve an increase in potassium conductance.

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
Buy now

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

Similar content being viewed by others

References

  1. Birkmayer, W. Spasticity—a Topical Survey (Huber, Vienna, 1972).

    Google Scholar 

  2. Curtis, D. R., Game, C. J. A., Johnston, G. A. R. & McCulloch, R. M. Brain Res. 70, 493–499 (1974).

    Article  CAS  Google Scholar 

  3. Davies, J. & Watkins, J. C. Brain Res. 70, 501–505 (1974).

    Article  CAS  Google Scholar 

  4. Olpe, H. R. et al. Eur. J. Pharmac. 52, 133–136 (1978).

    Article  CAS  Google Scholar 

  5. Bowery, N. G. et al. Eur. J. Pharmac. 71, 53–70 (1981).

    Article  CAS  Google Scholar 

  6. Kleinrok, A. & Kilbinger, H. Naunyn-Schmiedebergs Archs. Pharmak. 322, 216–220 (1983).

    Article  CAS  Google Scholar 

  7. Pierau, F. K. & Zimmermann, P. Brain Res. 54, 376–380 (1973).

    Article  CAS  Google Scholar 

  8. Davidoff, R. A. & Sears, E. Neurology 24, 957–963 (1974).

    Article  CAS  Google Scholar 

  9. Fox, S., Krnjevic, K., Morris, M. E., Puil, E. & Werman, R. Neuroscience 3, 495–515 (1978).

    Article  CAS  Google Scholar 

  10. Potashner, S. J. J. Neurochem. 32, 103–109 (1979).

    Article  CAS  Google Scholar 

  11. Bowery, N. G. et al. Nature 283, 92–94 (1980).

    Article  ADS  CAS  Google Scholar 

  12. Ault, B. & Evans, R. H. Eur. J. Pharmac. 71, 357–364 (1981).

    Article  CAS  Google Scholar 

  13. Collins, G. S., Anson, J. & Kelly, E. P. Brain Res. 238, 371–383 (1982).

    Article  CAS  Google Scholar 

  14. Shapovalov, A. I. & Shiriaev, B. E. Gen. Physiol. Biophys. 1, 423–433 (1982).

    Google Scholar 

  15. Dunlap, K. Br. J. Pharmac. 74, 579–585 (1981).

    Article  CAS  Google Scholar 

  16. Bowery, N. G., Hill, D. R. & Hudson, A. L. Br. J. Pharmac. 78, 191–206 (1983).

    Article  CAS  Google Scholar 

  17. Nicoll, R. A. & Alger, B. E. J. Neurosci, Meth. 4, 153–156 (1981).

    Article  CAS  Google Scholar 

  18. Lanthorn, T. H. & Cotman, C. W. Brain Res. 225, 171–178 (1981).

    Article  CAS  Google Scholar 

  19. Ault, B. & Nadler, J. V. J. Pharmac. exp. Ther. 223, 291–297 (1982).

    CAS  Google Scholar 

  20. Kandel, E. R., Spencer, W. A. & Brinley, F. J. J. Neurophysiol. 24, 225–242 (1961).

    Article  CAS  Google Scholar 

  21. Andersen, P., Eccles, J. C. & Løyning, Y. J. Neurophysiol. 27, 592–607 (1964).

    Article  CAS  Google Scholar 

  22. Eccles, J. C., Nicoll, R. A., Oshima, T. & Rubia, F. J. Proc. R. Soc. 198, 345–361 (1977).

    ADS  CAS  Google Scholar 

  23. Ben-Ari, Y., Krnjevic, K., Reiffenstein, R. J. & Reinhardt, W. Neuroscience 6, 2445–2463 (1981).

    Article  CAS  Google Scholar 

  24. Alger, B. E. & Nicoll, R. A. Science 210, 1122–1124 (1980).

    Article  ADS  CAS  Google Scholar 

  25. Hotson, J. & Prince, D. A. J. Neurophysiol. 43, 409–419 (1980).

    Article  CAS  Google Scholar 

  26. Schwartzkroin, P. A. & Stafstrom, C. E. Science 210, 1125–1127 (1980).

    Article  ADS  CAS  Google Scholar 

  27. Nicoll, R. A. & Alger, B. E. Science 212, 957–959 (1981).

    Article  ADS  CAS  Google Scholar 

  28. Thalmann, R. H. & Ayala, G. Y. Neurosci. Lett. 29, 243–248 (1982).

    Article  CAS  Google Scholar 

  29. Thalmann, R. H. Neurosci. Abstr. 8, 797 (1981).

    Google Scholar 

  30. Lancaster, B. & Wheal, H. V. J. Physiol., Lond. 334, 118P (1983).

    Google Scholar 

  31. Newberry, N. R. & Nicoll, R. A. J. Physiol., Lond. 348, 239–254 (1984).

    Article  CAS  Google Scholar 

  32. Blaxter, T. J. & Cottrell, G. A. J Physiol., Lond. 330, 46P (1982).

    CAS  Google Scholar 

Download references

Author information

Author notes

  1. N. R. Newberry

    Present address: Neuroscience Research Centre, Merck, Sharp & Dohme Ltd., Hertford Rd, Hoddeston, Hertfordshire, UK

Authors and Affiliations

  1. Departments of Pharmacology and Physiology, University of California, San Francisco, California, 94143, USA

    N. R. Newberry & R. A. Nicoll

Authors
  1. N. R. Newberry
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. A. Nicoll
    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

Newberry, N., Nicoll, R. Direct hyperpolarizing action of baclofen on hippocampal pyramidal cells. Nature 308, 450–452 (1984). https://doi.org/10.1038/308450a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/308450a0

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

Advanced 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