Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1979 Dec;67(4):563–568. doi: 10.1111/j.1476-5381.1979.tb08702.x

Selective antagonism by benzodiazepines of neuronal responses to excitatory amino acids in the cerebral cortex

JA Assumpção, N Bernardi, J Brown, TW Stone
PMCID: PMC2043902  PMID: 42460

Abstract

1 The recently discovered benzodiazepine receptor exists in high concentration in the cerebral cortex. We have, therefore, examined the effects of diazepam and chlordiazepoxide on cortical neurone responses to excitatory and inhibitory amino acids and acetylcholine, in the cortex of rats anaesthetized with urethane.

2 Chlordiazepoxide applied by microiontophoresis reduced the responses to glutamate and aspartate but acetylcholine responses were unaffected on most cells even by much higher doses of benzodiazepine. γ-Aminobutyric acid (GABA) and taurine responses were unaffected on most cells, but were reduced on 4 of 25 units. After intravenous diazepam, responses to GABA and taurine were reduced on 3 cells and unchanged on 11.

3 On Purkinje cells in the cerebellum a number of cells (5 of 16) exhibited a substantial increase in responses to GABA and taurine following intravenous or iontophoretic application of benzodiazepines.

4 It is suggested that the highly selective reduction of excitatory amino acid responses in the cerebral cortex may be of particular relevance to the behavioural effects of benzodiazepines.

Full text

PDF
563

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Burnstock G. Do some nerve cells release more than one transmitter? Neuroscience. 1976 Aug;1(4):239–248. doi: 10.1016/0306-4522(76)90054-3. [DOI] [PubMed] [Google Scholar]
  2. Choi D. W., Farb D. H., Fischbach G. D. Chlordiazepoxide selectively augments GABA action in spinal cord cell cultures. Nature. 1977 Sep 22;269(5626):342–344. doi: 10.1038/269342a0. [DOI] [PubMed] [Google Scholar]
  3. Costa E., Guidotti A., Mao C. C., Suria A. New concepts on the mechanism of action of benzodiazepines. Life Sci. 1975 Jul 15;17(2):167–185. doi: 10.1016/0024-3205(75)90501-9. [DOI] [PubMed] [Google Scholar]
  4. Curtis D. R., Johnston G. A. Amino acid transmitters in the mammalian central nervous system. Ergeb Physiol. 1974;69(0):97–188. doi: 10.1007/3-540-06498-2_3. [DOI] [PubMed] [Google Scholar]
  5. Curtis D. R., Lodge D., Johnston G. A., Brand S. J. Central actions of benzodiazepines. Brain Res. 1976 Dec 17;118(2):344–347. doi: 10.1016/0006-8993(76)90723-x. [DOI] [PubMed] [Google Scholar]
  6. Curtis D. R., Terbécis A. K. Bicuculline and thalamic inhibition. Exp Brain Res. 1972;16(2):210–218. doi: 10.1007/BF00233997. [DOI] [PubMed] [Google Scholar]
  7. Davies J., Polc P. Effect of a water soluble benzodiazepine on the responses of spinal neurones to acetylcholine and excitatory amino acid analogues. Neuropharmacology. 1978 Mar;17(3):217–220. doi: 10.1016/0028-3908(78)90104-1. [DOI] [PubMed] [Google Scholar]
  8. Dray A., Straughan D. W. Benzodiazepines: GABA and glycine receptors on single neurons in the rat medulla. J Pharm Pharmacol. 1976 Apr;28(4):314–315. doi: 10.1111/j.2042-7158.1976.tb04163.x. [DOI] [PubMed] [Google Scholar]
  9. Evans R. H., Francis A. A., Watkins J. C. Differential antagonism by chlorpromazine and diazepam of frog motoneurone depolarization induced by glutamate-related amino acids. Eur J Pharmacol. 1977 Aug 15;44(4):325–330. doi: 10.1016/0014-2999(77)90306-5. [DOI] [PubMed] [Google Scholar]
  10. Gallager D. W. Benzodiazepines: potentiation of a GABA inhibitory response in the dorsal raphe nucleus. Eur J Pharmacol. 1978 May 15;49(2):133–143. doi: 10.1016/0014-2999(78)90069-9. [DOI] [PubMed] [Google Scholar]
  11. Geller H. M., Taylor D. A., Hoffer B. J. Benzodiazepines and central inhibitory mechanisms. Naunyn Schmiedebergs Arch Pharmacol. 1978 Sep;304(2):81–88. doi: 10.1007/BF00495542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gähwiler B. H. Diazepam and chlordiazepoxide: powerful GABA antagonsits in explants of rat cerebellum. Brain Res. 1976 Apr 30;107(1):176–179. doi: 10.1016/0006-8993(76)90108-6. [DOI] [PubMed] [Google Scholar]
  13. Haefely W. E. Synaptic pharmacology of barbiturates and benzodiazepines. Agents Actions. 1977 Sep;7(3):353–359. doi: 10.1007/BF01969568. [DOI] [PubMed] [Google Scholar]
  14. Keller H. H., Schaffner R., Haefely W. Interaction of benzodiazepines with neuroleptics at central dopamine neurons. Naunyn Schmiedebergs Arch Pharmacol. 1976 Jul;294(1):1–7. doi: 10.1007/BF00692778. [DOI] [PubMed] [Google Scholar]
  15. Macdonald R., Barker J. L. Benzodiazepines specifically modulate GABA-mediated postsynaptic inhibition in cultured mammalian neurones. Nature. 1978 Feb 9;271(5645):563–564. doi: 10.1038/271563a0. [DOI] [PubMed] [Google Scholar]
  16. Marangos P. J., Paul S. M., Greenlaw P., Goodwin F. K., Skolnick P. Demonstration of an endogenous, competitive inhibitor(s) of [3H] diazepam binding in bovine brain. Life Sci. 1978 Jun 5;22(21):1893–1900. doi: 10.1016/0024-3205(78)90476-9. [DOI] [PubMed] [Google Scholar]
  17. Möhler H., Okada T., Heitz P., Ulrich J. Biochemical identification of the site of action of benzodiazepines in human brain by 3H-diazepam binding. Life Sci. 1978 Mar;22(11):985–995. doi: 10.1016/0024-3205(78)90364-8. [DOI] [PubMed] [Google Scholar]
  18. Polc P., Haefely W. Effects of two benzodiazepines, phenobarbitone, and baclofen on synaptic transmission in the cat cuneate nucleus. Naunyn Schmiedebergs Arch Pharmacol. 1976 Aug;294(2):121–131. doi: 10.1007/BF00507844. [DOI] [PubMed] [Google Scholar]
  19. Squires R. F., Brastrup C. Benzodiazepine receptors in rat brain. Nature. 1977 Apr 21;266(5604):732–734. doi: 10.1038/266732a0. [DOI] [PubMed] [Google Scholar]
  20. Steiner F. A., Felix D. Antagonistic effects of GABA and benzodiazepines on vestibular and cerebellar neurones. Nature. 1976 Mar 25;260(5549):346–347. doi: 10.1038/260346a0. [DOI] [PubMed] [Google Scholar]
  21. Stone T. W. Cortical pyramidal tract interneurones and their sensitivity to L-glutamic acid. J Physiol. 1973 Aug;233(1):211–225. doi: 10.1113/jphysiol.1973.sp010306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Stone T. W. Glutamate as the neurotransmitter of cerebellar granule cells in the rat: electrophysiological evidence. Br J Pharmacol. 1979 Jun;66(2):291–296. doi: 10.1111/j.1476-5381.1979.tb13678.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tsuchiya T., Fukushima H. Effects of benzodiazepines and pentobarbitone on the gaba-ergic recurrent inhibition of hippocampal neurons. Eur J Pharmacol. 1978 Apr 15;48(4):421–424. doi: 10.1016/0014-2999(78)90169-3. [DOI] [PubMed] [Google Scholar]
  24. Williamson M. J., Paul S. M., Skolnick P. Labelling of benzodiazepine receptors in vivo. Nature. 1978 Oct 12;275(5680):551–553. doi: 10.1038/275551a0. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES