Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1970 Sep;40(1):6–22. doi: 10.1111/j.1476-5381.1970.tb10606.x

Microinjections of tubocurarine, leptazol, strychnine and picrotoxin into the cerebral cortex of anaesthetized cats

U Banerjee, W Feldberg, V P Georgiev
PMCID: PMC1702708  PMID: 5487025

Abstract

1. In cats anaesthetized with intravenous chloralose, microinjections of tubocurarine, leptazol, strychnine or picrotoxin, in a volume of 1 μl, were made into the grey matter of the cerebral cortex and the electrical activity was recorded from the site of injection with the microinjection cannula which, insulated except at its tip, served as recording electrode.

2. Routinely the injections were made into the gyrus splenialis or into the underlying gyrus cinguli close to the mid-line, because the injections would then most likely be in grey and not in white matter. Injected in this way all four drugs set up foci of excitation which gave rise to synchronous firing of a large number of neurones with the result that high voltage negative spikes were recorded from the microinjection cannula.

3. On injection into the gyrus splenialis the threshold dose was about 0·04 μg for picrotoxin, about 0·2 μg for tubocurarine, about 5 μg for strychnine and 25 to 50 μg for leptazol. Following the injection of larger doses the spike discharge continued for a few hours after picrotoxin and tubocurarine, for over an hour after strychnine, but for a few minutes only after leptazol. On injection into the gyrus cinguli the threshold doses were slightly greater and with larger doses the spikes occurred at greater frequency but were of lower voltage than in the gyrus splenialis.

4. With large doses of picrotoxin injected into the gyrus splenialis the spikes developed an after-positivity and an after-discharge which sometimes passed into a short period of fast activity.

5. The foci of excitation set up by the drugs were restricted to the site of injection because on raising or lowering the microinjection cannula the spikes recorded from it quickly decreased in voltage and then disappeared. When the injections were made close to a sulcus and the microinjection cannula, on being lowered, traversed the sulcus, the spikes changed their polarity.

6. The spike discharge appears to be a consistent response to the injections of the drugs into grey matter of any part of the cerebral cortex since it was also obtained on their injection into the pyriform cortex, amygdala and area retrolimbica anterior, but not on their injection into white matter or caudate nucleus, thalamus or hypothalamus.

Full text

PDF
6

Selected References

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

  1. ANDERSEN P., ECCLES J. C., LOYNING Y., VOORHOEVE P. E. STRYCHNINE-RESISTANT INHIBITION IN THE BRAIN. Nature. 1963 Nov 30;200:843–845. doi: 10.1038/200843a0. [DOI] [PubMed] [Google Scholar]
  2. Aprison M. H., Werman R. The distribution of glycine in cat spinal cord and roots. Life Sci. 1965 Nov;4(21):2075–2083. doi: 10.1016/0024-3205(65)90325-5. [DOI] [PubMed] [Google Scholar]
  3. BRADLEY K., EASTON D. M., ECCLES J. C. An investigation of primary or direct inhibition. J Physiol. 1953 Dec 29;122(3):474–488. doi: 10.1113/jphysiol.1953.sp005015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BROOKS V. B., ASANUMA H. PHARMACOLOGICAL STUDIES OF RECURRENT CORTICAL INHIBITION AND FACILITATION. Am J Physiol. 1965 Apr;208:674–681. doi: 10.1152/ajplegacy.1965.208.4.674. [DOI] [PubMed] [Google Scholar]
  5. Baker W. W., Benedict F. Local electrographic responses to intrahippocampal d-tubocurarine and related neuromuscular blocking agents. Proc Soc Exp Biol Med. 1967 Feb;124(2):607–611. doi: 10.3181/00379727-124-31803. [DOI] [PubMed] [Google Scholar]
  6. Biscoe T. J., Curtis D. R. Strychnine and cortical inhibition. Nature. 1967 May 27;214(5091):914–915. doi: 10.1038/214914a0. [DOI] [PubMed] [Google Scholar]
  7. Brown R. D., Daigneault E. A., Pruett J. R. The effects of selected cholinergic drugs and strychine on cochlear responses and olivo-cochlear inhibition. J Pharmacol Exp Ther. 1969 Feb;165(2):300–309. [PubMed] [Google Scholar]
  8. CARMICHAEL E. A., FELDBERG W., FLEISCHHAUER K. The site of origin of the tremor produced by tubocurarine acting from the cerebral ventricles. J Physiol. 1962 Aug;162:539–554. doi: 10.1113/jphysiol.1962.sp006949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. CHANG H. T. Similarity in action between curare and strychnine on cortical neurons. J Neurophysiol. 1953 May;16(3):221–233. doi: 10.1152/jn.1953.16.3.221. [DOI] [PubMed] [Google Scholar]
  10. CHATFIELD P. O., PURPURA D. P., CHAMBERS D. M. Augmentation of evoked cortical potentials by topical application of prostigmine and acetylcholine after atropinization of cortex. Electroencephalogr Clin Neurophysiol. 1954 May;6(2):287–298. doi: 10.1016/0013-4694(54)90030-9. [DOI] [PubMed] [Google Scholar]
  11. CRAWFORD J. M., CURTIS D. R., VOORHOEVE P. E., WILSON V. J. STRYCHNINE AND CORTICAL INHIBITION. Nature. 1963 Nov 30;200:845–846. doi: 10.1038/200845a0. [DOI] [PubMed] [Google Scholar]
  12. CURTIS D. R. Pharmacological investigations upon inhibition of spinal motoneurones. J Physiol. 1959 Jan 28;145(1):175–192. doi: 10.1113/jphysiol.1959.sp006134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Curtis D. R., Hösli L., Johnston G. A. A pharmacological study of the depression of spinal neurones by glycine and related amino acids. Exp Brain Res. 1968;6(1):1–18. doi: 10.1007/BF00235443. [DOI] [PubMed] [Google Scholar]
  14. Curtis D. R., Hösli L., Johnston G. A. Inhibition of spinal neurons by glycine. Nature. 1967 Sep 30;215(5109):1502–1503. doi: 10.1038/2151502a0. [DOI] [PubMed] [Google Scholar]
  15. DESMEDT J. E., MONACO P. Mode of action of the efferent olivo-cochlear bundle on the inner ear. Nature. 1961 Dec 30;192:1263–1265. doi: 10.1038/1921263a0. [DOI] [PubMed] [Google Scholar]
  16. DESMEDT J. E., MONACO P. [Suppression by strychnine of the centrifugal inhibitory effect exerted by the olivocochlear bundle]. Arch Int Pharmacodyn Ther. 1960 Dec 1;129:244–248. [PubMed] [Google Scholar]
  17. Davidoff R. A., Graham L. T., Jr, Shank R. P., Werman R., Aprison M. H. Changes in amino acid concentrations associated with loss of spinal interneurons. J Neurochem. 1967 Oct;14(10):1025–1031. doi: 10.1111/j.1471-4159.1967.tb09513.x. [DOI] [PubMed] [Google Scholar]
  18. ECCLES J. C., FATT P., KOKETSU K. Cholinergic and inhibitory synapses in a pathway from motor-axon collaterals to motoneurones. J Physiol. 1954 Dec 10;126(3):524–562. doi: 10.1113/jphysiol.1954.sp005226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. FELDBERG W., FLEISCHAUER K. Scratching movements evoked by drugs applied to the upper cervical cord. J Physiol. 1960 Jun;151:502–517. doi: 10.1113/jphysiol.1960.sp006456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. FELDBERG W., FLEISCHHAUER K. THE HIPPOCAMPUS AS THE SITE OF ORIGIN OF THE SEIZURE DISCHARGE PRODUCED BY TUBOCURARINE ACTING FROM THE CEREBRAL VENTRICLES. J Physiol. 1963 Sep;168:435–442. doi: 10.1113/jphysiol.1963.sp007201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. FELDBERG W., FLEISCHHAUER K. The site of origin of the seizure discharge produced by tubocurarine acting from the cerebral ventricles. J Physiol. 1962 Feb;160:258–283. doi: 10.1113/jphysiol.1962.sp006845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Feldberg W., Fleischhauer K. Site of origin of the abnormal discharge in the electrocorticogram produced by tubocurarine perfused through the anterior horn of a lateral ventricle. J Physiol. 1967 Aug;191(3):487–500. doi: 10.1113/jphysiol.1967.sp008263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Feldberg W., Georgiev V. P. Central effects of picrotoxin when acting from the liquor spaces in anaesthetized cats. Br J Pharmacol. 1970 Sep;40(1):23–36. doi: 10.1111/j.1476-5381.1970.tb10607.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Feldberg W., Hall G. H., Reit E. Effects of Reichstein's compound S, strychnine and leptazol perfused through cerebral ventricles of cats. Br J Pharmacol Chemother. 1966 Nov;28(2):182–196. doi: 10.1111/j.1476-5381.1966.tb01884.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. GREEN J. D., MANCIA M., von BAUMGARTEN Recurrent inhibition in the olfactory bulb. I. Effects of antidromic stimulation of the lateral olfactory tract. J Neurophysiol. 1962 Jul;25:467–488. doi: 10.1152/jn.1962.25.4.467. [DOI] [PubMed] [Google Scholar]
  26. GRUNDFEST H., PURPURA D. P. Nature of dendritic potentials and synaptic mechanisms in cerebral cortex of cat. J Neurophysiol. 1956 Nov;19(6):573–595. doi: 10.1152/jn.1956.19.6.573. [DOI] [PubMed] [Google Scholar]
  27. Graham L. T., Jr, Shank R. P., Werman R., Aprison M. H. Distribution of some synaptic transmitter suspects in cat spinal cord: glutamic acid, aspartic acid, gamma-aminobutyric acid, glycine and glutamine. J Neurochem. 1967 Apr;14(4):465–472. doi: 10.1111/j.1471-4159.1967.tb09545.x. [DOI] [PubMed] [Google Scholar]
  28. KLUVER H., BARRERA E. A method for the combined staining of cells and fibers in the nervous system. J Neuropathol Exp Neurol. 1953 Oct;12(4):400–403. doi: 10.1097/00005072-195312040-00008. [DOI] [PubMed] [Google Scholar]
  29. Katsuki Y., Tanaka Y., Miyoshi T. Action of acetylcholine on cochlear responses. Nature. 1965 Jul 3;207(992):32–34. doi: 10.1038/207032a0. [DOI] [PubMed] [Google Scholar]
  30. Krnjević K., Randić M., Straughan D. W. Pharmacology of cortical inhibition. J Physiol. 1966 May;184(1):78–105. doi: 10.1113/jphysiol.1966.sp007904. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. MORLOCK N., WARD A. A., Jr The effects of curare on cortical activity. Electroencephalogr Clin Neurophysiol. 1961 Feb;13:60–67. doi: 10.1016/0013-4694(61)90075-x. [DOI] [PubMed] [Google Scholar]
  32. McKinstry D. N., Koelle G. B. Inhibition of release of acetylcholine by strychnine and its implications regarding transmission by the olivo-cochlear bundle. Nature. 1967 Feb 4;213(5075):505–506. doi: 10.1038/213505a0. [DOI] [PubMed] [Google Scholar]
  33. POLLEN D. A., MARSAN C. A. CORTICAL INHIBITORY POSTSYNAPTIC POTENTIALS AND STRYCHNINIZATION. J Neurophysiol. 1965 Mar;28:342–358. doi: 10.1152/jn.1965.28.2.342. [DOI] [PubMed] [Google Scholar]
  34. PURPURA D. P., GRUNDFEST H. Physiological and pharmacological consequences of different synaptic organizations in cerebral and cerebellar cortex of cat. J Neurophysiol. 1957 Sep;20(5):494–522. doi: 10.1152/jn.1957.20.5.494. [DOI] [PubMed] [Google Scholar]
  35. Phillis J. W., York D. H. Pharmacological studies on a cholinergic inhibition in the cerebral cortex. Brain Res. 1968 Sep;10(3):297–306. doi: 10.1016/0006-8993(68)90201-1. [DOI] [PubMed] [Google Scholar]
  36. Phillis J. W., York D. H. Strychnine block of neural and drug-induced inhibition in the cerebral cortex. Nature. 1967 Dec 2;216(5118):922–923. doi: 10.1038/216922a0. [DOI] [PubMed] [Google Scholar]
  37. Pollen D. A., Lux H. D. Conductance changes during inhibitory postsynaptic potentials in normal and strychninized cortical neurons. J Neurophysiol. 1966 May;29(3):369–381. doi: 10.1152/jn.1966.29.3.369. [DOI] [PubMed] [Google Scholar]
  38. STEFANIS C., JASPER H. STRYCHNINE REVERSAL OF INHIBITORY POTENTIALS IN PYRAMIDAL TRACT NEURONES. Int J Neuropharmacol. 1965 May;4:125–138. doi: 10.1016/0028-3908(65)90002-x. [DOI] [PubMed] [Google Scholar]
  39. SUZUKI H., TUKAHARA Y. RECURRENT INHIBITION OF THE BETZ CELL. Jpn J Physiol. 1963 Aug 15;13:386–398. doi: 10.2170/jjphysiol.13.386. [DOI] [PubMed] [Google Scholar]
  40. Sawa M., Maruyama N., Kaji S., Nakamura K. Action of strychnine to cortical neurons. Jpn J Physiol. 1966 Apr 15;16(2):126–141. doi: 10.2170/jjphysiol.16.126. [DOI] [PubMed] [Google Scholar]
  41. Werman R., Davidoff R. A., Aprison M. H. Inhibition of motoneurones by iontophoresis of glycine. Nature. 1967 May 13;214(5089):681–683. doi: 10.1038/214681a0. [DOI] [PubMed] [Google Scholar]
  42. Werman R., Davidoff R. A., Aprison M. H. Inhibitory of glycine on spinal neurons in the cat. J Neurophysiol. 1968 Jan;31(1):81–95. doi: 10.1152/jn.1968.31.1.81. [DOI] [PubMed] [Google Scholar]
  43. von BAUMGARTEN, GREEN J. D., MANCIA M. Recurrent inhibition in the olfactory bulb. II. Effects of antidromic stimulation of commissural fibers. J Neurophysiol. 1962 Jul;25:489–500. doi: 10.1152/jn.1962.25.4.489. [DOI] [PubMed] [Google Scholar]

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

RESOURCES