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. 1971 May;42(1):88–99. doi: 10.1111/j.1476-5381.1971.tb07089.x

Depletion of brain noradrenaline and dopamine by 6-hydroxydopamine

G R Breese, T D Traylor
PMCID: PMC1666995  PMID: 5580702

Abstract

1. After intracisternal administration, 6-hydroxydopamine had a greater effect on brain noradrenaline than on dopamine.

2. Administration of two doses of 6-hydroxydopamine increased the depletion of noradrenaline but not of dopamine.

3. Small doses of 6-hydroxydopamine decreased the concentration of noradrenaline with little or no effect on dopamine. Tyrosine hydroxylase activity was not reduced with these treatments.

4. While pargyline pretreatment offered no advantage in the depletion of brain noradrenaline after 6-hydroxydopamine, depletion of brain dopamine was greatly potentiated by this treatment. The reduction of striatal tyrosine hydroxylase activity observed after 6-hydroxydopamine was also potentiated by pargyline pretreatment.

5. The amounts of labelled noradrenaline and dopamine formed from 3H-tyrosine were greatly reduced by 6-hydroxydopamine treatment. After 3H-DOPA, formation of noradrenaline was greatly reduced while formation of labelled dopamine was only moderately reduced suggesting that decarboxylation of DOPA can occur in other than catecholamine containing neurones.

6. Desmethylimipramine and imipramine inhibited depletion of noradrenaline produced by 6-hydroxydopamine but did not alter depletion of dopamine. Reserpine did not inhibit depletion of catecholamines produced by 6-hydroxydopamine.

7. Administration of 6-hydroxydopamine to developing rats lowered both noradrenaline and dopamine concentrations as well as the tyrosine hydroxylase activity in the brains of these animals.

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Selected References

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

  1. ANTON A. H., SAYRE D. F. A study of the factors affecting the aluminum oxide-trihydroxyindole procedure for the analysis of catecholamines. J Pharmacol Exp Ther. 1962 Dec;138:360–375. [PubMed] [Google Scholar]
  2. ANTON A. H., SAYRE D. F. THE DISTRIBUTION OF DOPAMINE AND DOPA IN VARIOUS ANIMALS AND A METHOD FOR THEIR DETERMINATION IN DIVERSE BIOLOGICAL MATERIAL. J Pharmacol Exp Ther. 1964 Sep;145:326–336. [PubMed] [Google Scholar]
  3. Agrawal H. C., Glisson S. N., Himwich W. A. Changes in monoamines of rat brain during postnatal ontogeny. Biochim Biophys Acta. 1966 Dec 28;130(2):511–513. doi: 10.1016/0304-4165(66)90247-9. [DOI] [PubMed] [Google Scholar]
  4. Angeletti P. U., Levi-Montalcini R. Sympathetic nerve cell destruction in newborn mammals by 6-hydroxydopamine. Proc Natl Acad Sci U S A. 1970 Jan;65(1):114–121. doi: 10.1073/pnas.65.1.114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bennett T., Burnstock G., Cobb J. L., Malmfors T. An ultrastructural and histochemical study of the short-term effects of 6-hydroxydopamine on adrenergic nerves in the domestic fowl. Br J Pharmacol. 1970 Apr;38(4):802–809. doi: 10.1111/j.1476-5381.1970.tb09889.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bloom F. E., Algeri S., Groppetti A., Revuelta A., Costa E. Lesions of central norepinephrine terminals with 6-OH-dopamine: biochemistry and fine structure. Science. 1969 Dec 5;166(3910):1284–1286. doi: 10.1126/science.166.3910.1284. [DOI] [PubMed] [Google Scholar]
  7. Breese G. R., Chase T. N., Kopin I. J. Effect of monoamine oxidase inhibitors on the disposition of intracisternally administered metaraminol-3H. Biochem Pharmacol. 1970 Feb;19(2):525–532. doi: 10.1016/0006-2952(70)90209-1. [DOI] [PubMed] [Google Scholar]
  8. Breese G. R., Chase T. N., Kopin I. J. Metabolism of tyramine-3H and octopamine-3H by rat brain. Biochem Pharmacol. 1969 Apr;18(4):863–869. doi: 10.1016/0006-2952(69)90057-4. [DOI] [PubMed] [Google Scholar]
  9. Breese G. R., Kopin I. J., Weise V. K. Effects of amphetamine derivatives on brain dopamine and noradrenaline. Br J Pharmacol. 1970 May;38(3):537–545. doi: 10.1111/j.1476-5381.1970.tb10595.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Breese G. R., Traylor T. D. Effect of 6-hydroxydopamine on brain norepinephrine and dopamine evidence for selective degeneration of catecholamine neurons. J Pharmacol Exp Ther. 1970 Sep;174(3):413–420. [PMC free article] [PubMed] [Google Scholar]
  11. Burkard W. P., Jalfre M., Blum J. Effect of 6-hydroxydopamine on behaviour and cerebral amine content in rats. Experientia. 1969 Dec 15;25(12):1295–1296. doi: 10.1007/BF01897508. [DOI] [PubMed] [Google Scholar]
  12. CARLSSON A. The occurrence, distribution and physiological role of catecholamines in the nervous system. Pharmacol Rev. 1959 Jun;11(2 Pt 2):490–493. [PubMed] [Google Scholar]
  13. CARLSSON A., WALDECK B. INHIBITION OF 3H-METARAMINOL UPTAKE BY ANTIDEPRESSIVE AND RELATED AGENTS. J Pharm Pharmacol. 1965 Apr;17:243–244. doi: 10.1111/j.2042-7158.1965.tb07653.x. [DOI] [PubMed] [Google Scholar]
  14. Evetts K. D., Iversen L. L. Effects of protriptyline on the depletion of catecholamines induced by 6-hydroxydopamine in the brain of the rat. J Pharm Pharmacol. 1970 Jul;22(7):540–543. doi: 10.1111/j.2042-7158.1970.tb10564.x. [DOI] [PubMed] [Google Scholar]
  15. Evetts K. D., Uretsky N. J., Iversen L. L., Iversen S. D. Effects of 6-hydroxydopamine on CNS catecholamines, spontaneous motor activity and amphetamine induced hyperactivity in rats. Nature. 1970 Mar 7;225(5236):961–962. doi: 10.1038/225961a0. [DOI] [PubMed] [Google Scholar]
  16. Fuxe K., Ungerstedt U. Histochemical studies on the effect of (positive)-amphetamine, drugs of the imipramine group and tryptamine on central catecholamine and 5-hydroxytryptamine neurons after intraventricular injection of catecholamines and 5-hydroxytryptamine. Eur J Pharmacol. 1968 Sep;4(2):135–144. doi: 10.1016/0014-2999(68)90169-6. [DOI] [PubMed] [Google Scholar]
  17. HAEGGENDAL J. AN IMPROVED METHOD FOR FLUORIMETRIC DETERMINATION OF SMALL AMOUNTS OF ADRENALINE AND NORADRENALINE IN PLASMA AND TISSUES. Acta Physiol Scand. 1963 Nov;59:242–254. doi: 10.1111/j.1748-1716.1963.tb02739.x. [DOI] [PubMed] [Google Scholar]
  18. Hökfelt T., Ungerstedt U. Electron and fluorescence microscopical studies on the nucleus caudatus putamen of the rat after unilateral lesions of ascending nigro-neostriatal dopamine neurons. Acta Physiol Scand. 1969 Aug;76(4):415–426. doi: 10.1111/j.1748-1716.1969.tb04489.x. [DOI] [PubMed] [Google Scholar]
  19. LAVERTY R., SHARMAN D. F., VOGT M. ACTION OF 2, 4, 5-TRIHYDROXYPHENYLETHYLAMINE ON THE STORAGE AND RELEASE OF NORADRENALINE. Br J Pharmacol Chemother. 1965 Apr;24:549–560. doi: 10.1111/j.1476-5381.1965.tb01745.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Malmfors T., Sachs C. Degeneration of adrenergic nerves produced by 6-hydroxydopamine. Eur J Pharmacol. 1968 Apr;3(1):89–92. doi: 10.1016/0014-2999(68)90056-3. [DOI] [PubMed] [Google Scholar]
  21. Mueller R. A., Thoenen H., Axelrod J. Adrenal tyrosine hydroxylase: compensatory increase in activity after chemical sympathectomy. Science. 1969 Jan 31;163(3866):468–469. doi: 10.1126/science.163.3866.468. [DOI] [PubMed] [Google Scholar]
  22. Musacchio J. M., Julou L., Kety S. S., Glowinski J. Increase in rat brain tyrosine hydroxylase activity produced by electroconvulsive shock. Proc Natl Acad Sci U S A. 1969 Aug;63(4):1117–1119. doi: 10.1073/pnas.63.4.1117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. NAGATSU T., LEVITT M., UDENFRIEND S. A RAPID AND SIMPLE RADIOASSAY FOR TYROSINE HYDROXYLASE ACTIVITY. Anal Biochem. 1964 Sep;9:122–126. doi: 10.1016/0003-2697(64)90092-2. [DOI] [PubMed] [Google Scholar]
  24. PORTER C. C., TOTARO J. A., STONE C. A. Effect of 6-hydroxydopamine and some other compounds on the concentration of norepinephrine in the hearts of mice. J Pharmacol Exp Ther. 1963 Jun;140:308–316. [PubMed] [Google Scholar]
  25. Schanberg S. M., Schildkraut J. J., Breese G. R., Kopin I. J. Metabolism of normetanephrine-H3 in rat brain--identification of conjugated 3-methoxy-4-hydrophenylglycol as the major metabolite. Biochem Pharmacol. 1968 Feb;17(2):247–254. doi: 10.1016/0006-2952(68)90330-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schanberg S. M., Schildkraut J. J., Kopin I. J. The effects of psychoactive drugs on norepinephrine-3-H metabolism in brain. Biochem Pharmacol. 1967 Feb;16(2):393–399. doi: 10.1016/0006-2952(67)90040-8. [DOI] [PubMed] [Google Scholar]
  27. Sedvall G. C., Weise V. K., Kopin I. J. The rate of norepinephrine synthesis measured in vivo during short intervals; influence of adrenergic nerve impulse activity. J Pharmacol Exp Ther. 1968 Feb;159(2):274–282. [PubMed] [Google Scholar]
  28. Thoenen H., Tranzer J. P. Chemical sympathectomy by selective destruction of adrenergic nerve endings with 6-Hydroxydopamine. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1968;261(3):271–288. doi: 10.1007/BF00536990. [DOI] [PubMed] [Google Scholar]
  29. Tranzer J. P., Thoenen H. An electron microscopic study of selective, acute degeneration of sympathetic nerve terminals after administration of 6-hydroxydopamine. Experientia. 1968 Feb 15;24(2):155–156. doi: 10.1007/BF02146956. [DOI] [PubMed] [Google Scholar]
  30. Ungerstedt U. 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur J Pharmacol. 1968 Dec;5(1):107–110. doi: 10.1016/0014-2999(68)90164-7. [DOI] [PubMed] [Google Scholar]
  31. Uretsky N. J., Iversen L. L. Effects of 6-hydroxydopamine on catecholamine containing neurones in the rat brain. J Neurochem. 1970 Feb;17(2):269–278. doi: 10.1111/j.1471-4159.1970.tb02210.x. [DOI] [PubMed] [Google Scholar]

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