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. 1982 Jul;76(3):403–411. doi: 10.1111/j.1476-5381.1982.tb09234.x

Reversible effects of tetanus toxin on striatal-evoked responses and [3H]-gamma-aminobutyric acid release in the rat substantia nigra.

G L Collingridge, J Davies
PMCID: PMC2071811  PMID: 6286022

Abstract

1 The effects of sublethal doses of tetanus toxin on gamma-aminobutyric acid (GABA)-mediated synaptic transmission and [3H]-GABA release were studied in the rat substantia nigra. 2 Intranigral injections of tetanus toxin at 1-5 times the mouse LD50 dose produced ipsiversive circling behaviour which was maximal after 1 week and lasted 2-3 weeks. Rats then displayed normal behavior suggesting that the effects of the toxin were fully reversible. 3 In the treated nigra of circling rats there was a reduction in the striatal-evoked inhibition of compacta and reticulata neurones, but no change in their spontaneous firing rates. Some forms of striatal-evoked excitation were also reduced. Once rats had recovered from circling no alterations in the synaptic responses were detected. 4 In circling rats there were no differences in the sensitivities of neurones in the treated and untreated nigra to GABA or to other inhibitory neurotransmitters. 5 The Ca2+-dependent, K+-evoked release of [3H]-GABA from slices prepared from the treated nigra of circling rats was less than that from the untreated nigra of circling rats. No differences in nigral [3H]-GABA release were observed once rats had recovered from the circling behaviour. 6 The results demonstrate that doses of tetanus toxin which produce reversible behavioural effects can interfere reversibly with GABA-mediated synaptic transmission by a presynaptic mechanism which probably involves a reduction in transmitter release.

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Selected References

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  1. 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]
  2. BROOKS V. B., CURTIS D. R., ECCLES J. C. The action of tetanus toxin on the inhibition of motoneurones. J Physiol. 1957 Mar 11;135(3):655–672. doi: 10.1113/jphysiol.1957.sp005737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bigalke H., Heller I., Bizzini B., Habermann E. Tetanus toxin and botulinum A toxin inhibit release and uptake of various transmitters, as studied with particulate preparations from rat brain and spinal cord. Naunyn Schmiedebergs Arch Pharmacol. 1981 Jun;316(3):244–251. doi: 10.1007/BF00505657. [DOI] [PubMed] [Google Scholar]
  4. CARREA R., LANARI A. Chronic effect of tetanus toxin applied locally to the cerebral cortex of the dog. Science. 1962 Aug 3;137(3527):342–343. doi: 10.1126/science.137.3527.342. [DOI] [PubMed] [Google Scholar]
  5. Collingridge G. L., Collins G. G., Davies J., James T. A., Neal M. J., Tongroach P. Effect of tetanus toxin on transmitter release from substantia nigra and striatum in vitro. J Neurochem. 1980 Mar;34(3):540–547. doi: 10.1111/j.1471-4159.1980.tb11178.x. [DOI] [PubMed] [Google Scholar]
  6. Collingridge G. L., Davies J. Reversible effects of low doses of tetanus toxin on synaptic inhibition in the substantia nigra and turning behaviour in the rat. Brain Res. 1980 Mar 10;185(2):455–459. doi: 10.1016/0006-8993(80)91086-0. [DOI] [PubMed] [Google Scholar]
  7. Collingridge G. L., Davies J. The influence of striatal stimulation and putative neurotransmitters on identified neurones in the rat substantia nigra. Brain Res. 1981 May 18;212(2):345–359. doi: 10.1016/0006-8993(81)90467-4. [DOI] [PubMed] [Google Scholar]
  8. Collingridge G. L., James T. A., MacLeod N. K. Antidromic latency variations of nigral compacta neurones. Experientia. 1980 Aug 15;36(8):970–971. doi: 10.1007/BF01953825. [DOI] [PubMed] [Google Scholar]
  9. Collingridge G. L., Thompson P. A., Davies J., Mellanby J. In vitro effect of tetanus toxin on GABA release form rat hippocampal slices. J Neurochem. 1981 Oct;37(4):1039–1041. doi: 10.1111/j.1471-4159.1981.tb04492.x. [DOI] [PubMed] [Google Scholar]
  10. Curtis D. R., De Groat W. C. Tetanus toxin and spinal inhibition. Brain Res. 1968 Aug 26;10(2):208–212. doi: 10.1016/0006-8993(68)90123-6. [DOI] [PubMed] [Google Scholar]
  11. Davies J., Tongroach P. Tetanus toxin and synaptic inhibition in the substantia nigra and striatum of the rat. J Physiol. 1979 May;290(2):23–36. doi: 10.1113/jphysiol.1979.sp012756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dray A., Gonye T. J., Oakley N. R. Caudate stimulation and substantia nigra activity in the rat. J Physiol. 1976 Aug;259(3):825–849. doi: 10.1113/jphysiol.1976.sp011497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dray A. The striatum and substantia nigra: a commentary on their relationships. Neuroscience. 1979;4(10):1407–1439. doi: 10.1016/0306-4522(79)90048-4. [DOI] [PubMed] [Google Scholar]
  14. Gale K., Iadarola M. J. GABAergic denervation of rat substantia nigra: functional and pharmacological properties. Brain Res. 1980 Feb 3;183(1):217–223. doi: 10.1016/0006-8993(80)90133-x. [DOI] [PubMed] [Google Scholar]
  15. Hagenah R., Benecke R., Wiegand H. Effects of type A botulinum toxin on the cholinergic transmission at spinal Renshaw cells and on the inhibitory action at Ia inhibitory interneurones. Naunyn Schmiedebergs Arch Pharmacol. 1977 Oct;299(3):267–272. doi: 10.1007/BF00500319. [DOI] [PubMed] [Google Scholar]
  16. Hill R. G., Simmonds M. A., Straughan D. W. Antagonism of gamma-aminobutyric acid and glycine by convulsants in the cuneate nucleus of cat. Br J Pharmacol. 1976 Jan;56(1):9–19. doi: 10.1111/j.1476-5381.1976.tb06952.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Imperato A., Porceddu M. L., Morelli M., Faa G., Di Chiara G. Role of dorsal mesencephalic reticular formation and deep layers of superior colliculus as out-put stations for turning behaviour elicited from the substantia nigra pars reticulata. Brain Res. 1981 Jul 20;216(2):437–443. doi: 10.1016/0006-8993(81)90146-3. [DOI] [PubMed] [Google Scholar]
  18. James T. A., Collingridge G. L. Rapid behavioural and biochemical effects of tetanus toxin microinjected into the substantia nigra: a dual role for GABA? Neurosci Lett. 1979 Feb;11(2):205–208. doi: 10.1016/0304-3940(79)90129-0. [DOI] [PubMed] [Google Scholar]
  19. Kilpatrick I. C., Collingridge G. L., Starr M. S. Evidence for the participation of nigrotectal gamma-aminobutyrate-containing neurones in striatal and nigral-derived circling in the rat. Neuroscience. 1982 Jan;7(1):207–222. doi: 10.1016/0306-4522(82)90161-0. [DOI] [PubMed] [Google Scholar]
  20. Kilpatrick I. C., Starr M. S., Fletcher A., James T. A., MacLeod N. K. Evidence for a GABAergic nigrothalamic pathway in the rat. I. Behavioural and biochemical studies. Exp Brain Res. 1980;40(1):45–54. doi: 10.1007/BF00236661. [DOI] [PubMed] [Google Scholar]
  21. Kilpatrick I. C., Starr M. S. Involvement of dopamine in circling responses to muscimol depends on intranigral site of injection. Eur J Pharmacol. 1981 Feb 19;69(4):407–419. doi: 10.1016/0014-2999(81)90444-1. [DOI] [PubMed] [Google Scholar]
  22. McGeer P. L., McGeer E. G., Campbell J. J. Rotatory effects of intracerebral tetanus toxin injections. Exp Neurol. 1980 Feb;67(2):363–367. doi: 10.1016/0014-4886(80)90235-6. [DOI] [PubMed] [Google Scholar]
  23. Osborne R. H., Bradford H. F., Jones D. G. Patterns of amino acid release from nerve-endings isolated from spinal cord and medulla. J Neurochem. 1973 Aug;21(2):407–419. doi: 10.1111/j.1471-4159.1973.tb04260.x. [DOI] [PubMed] [Google Scholar]
  24. Pycock C. J. Turning behaviour in animals. Neuroscience. 1980;5(3):461–514. doi: 10.1016/0306-4522(80)90048-2. [DOI] [PubMed] [Google Scholar]
  25. Srinivasan V., Neal M. J., Mitchell J. F. The effect of electrical stimulation and high potassium concentrations on the efflux of (3H) gamma-aminobutyric acid from brain slices. J Neurochem. 1969 Aug;16(8):1235–1244. doi: 10.1111/j.1471-4159.1969.tb05971.x. [DOI] [PubMed] [Google Scholar]

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