Degenerative effects of 6-aminodopamine and 6-hydroxydopamine on peripheral adrenergic nerves

  • George R. Siggins
  • David S. Forman


A 6-hydroxydopamine analogue, 6-aminodopamine (6-ADA), was compared with 6-hydroxydopamine (6-OHDA) as a potential agent for chemical sympathectomy. The adrenergic terminals innervating arterioles of the frog retrolingual membrane were used as a test system. Four days after two topical treatments with 0.25 mg/ml of either drug, most of the periarteriolar adrenergic nerves demonstrated swelling, fiber disruption, or a bright beaded appearance in the fluorescence microscope. Treatment with 0.5 mg/ml 6-OHDA abolished all fluorescence. After 0.5 mg/ml 6-ADA, no normal adrenergic fibers were seen, although a few fibers survived and exhibited a beaded appearance. In contrast to 6-OHDA, this higher dose of 6-ADA produced some signs of general tissue toxicity. After treatment with either drug, electron microscopy revealed adrenergic nerves with large electron-opaque structures containing the degenerated remains of large granular vesicles. Nerve areas which contained the degenerating structures occasionally alternated with swollen axonal regions containing many microtubules but no vesicles. Cholinergic nerves showed no evidence of damage. These results suggest that 6-ADA selectively destroys peripheral adrenergic nerves much like 6-OHDA, providing an additional marker for the ultrastructural identification of adrenergic nerves. Their analogous chemical suggest a similar metabolic mechanism for destruction of adrenergic nerves.

Key words

Adrenergic nerves, arterioles Chemical sympathectomy 6-aminodopamine, 6-hydroxydopamine Fluorescence histochemistry Electron microscopy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Azuma, T., Binia, A., Visscher, M. B.: Adrenergic mechanisms in the bullfrog and turtle. Amer. J. Physiol.209, 1287–1294 (1965)PubMedGoogle Scholar
  2. Baumgarten, H. G., Björklund, A., Lachenmayer, L., Nobin, A., Stenevi, V.: Long-lasting selective depletion of brain serotonin by 5,6-dihydroxytryptamine. Acta physiol. scand., Suppl.373, (1971)Google Scholar
  3. Berman, H. J., Siggins, G. R.: Neurogenic factors in the microvascular system. Fed. Proc.27, 1384–1390 (1968)PubMedGoogle Scholar
  4. Blank, C. L., Kissinger, P. T., Adams, R. N.: 5,6-Dihydroxyindole formation from oxidized 6-hydroxydopamine. Europ. J. Pharmacol.19, 391–394 (1972a)Google Scholar
  5. Blank, C. L., Murrill, E., Adams, R. N.: Central nervous system effects of 6-aminodopamine and 6-hydroxydopamine. Brain Res.45, 635–637 (1972b)CrossRefPubMedGoogle Scholar
  6. Bloom, F. E., Algeri, S., Groppetti, A., Revuelta, A., Costa, E.: Selective lesion of central norepinephrine terminals with 6-OH dopamine: combined biochemical and fine structural analysis. Science166, 1284–1286 (1969)PubMedGoogle Scholar
  7. Falck, B., Häggendal, J., Owman, Ch.: The localization of adrenaline in adrenergic nerves in the frog. Quart. J. exp. Physiol.48, 253–257 (1963)Google Scholar
  8. Falck, B., Hillarp, N. A., Thieme, G., Torp, A.: Fluorescence of catecholamines and related compounds condensed with formaldehyde. J. Histochem. Cytochem.10, 349–354 (1962)Google Scholar
  9. Heikkila, R., Cohen, G.: Inhibition of biogenic amine uptake by hydrogen peroxide: a mechanism for toxic effects of 6-hydroxydopamine. Science172, 1257–1258 (1971)PubMedGoogle Scholar
  10. Heikkila, R. E., Cohen, G.:In vivo generation of hydrogen peroxide from 6-hydroxydopamine. Experientia (Basel)28, 1197 (1972)Google Scholar
  11. Heikkila, R. E., Mytilineou, C., Côté, L., Cohen, G.: Evidence for degeneration of sympathetic nerve terminals caused by the ortho-and para-quinones of 6-hydroxydopamine. J. Neurochem.20, 1345–1350 (1973)PubMedGoogle Scholar
  12. Jonsson, G.: Quantitation of fluorescence of biogenic monoamines. Progr. Histochem. Cytochem.2, 299–334 (1971)Google Scholar
  13. Malmfors, T., Sachs, C.: Degeneration of adrenergic nerves produced by 6-hydroxydopamine. Europ. J. Pharmacol.3, 89–92 (1968)Google Scholar
  14. Powell, W. S., Heacock, R. S.: The oxidation of 6-hydroxydopamine. J. Pharm. Pharmacol.25, 193–200 (1973)PubMedGoogle Scholar
  15. Sachs, C.: Failure of 6-hydroxynoradrenaline to produce degeneration of catecholamine neurons. Europ. J. Pharmacol.20, 149–155 (1972)Google Scholar
  16. Saner, A., Thoenen, H. T.: Model experiments on the molecular mechanism of action of 6-hydroxydopamine. Molec. Pharmacol.7, 147–154 (1971)Google Scholar
  17. Siggins, G. R.: Nervous control of the arterioles in the retrolingual membrane of the frog (Rana pipiens). Doctoral dissertation, Boston University Graduate School (1967)Google Scholar
  18. Siggins, G. R., Bloom, F. E.: Cytochemical and physiological effects of 6-hydroxydopamine on periarteriolar nerves of frogs. Circulat. Res.27, 23–38 (1970)PubMedGoogle Scholar
  19. Siggins, G. R., Forman, D. S., Bloom, F. E., Sims K. L., Adams, R. N.: Destruction of peripheral and central adrenergic nerves by 6-aminodopamine (6-ADA). Fed. Proc.32, 692 (1973)Google Scholar
  20. Siggins, G. R., Weitsen, H. A.: Cytochemical and physiological evidence for cholinergic, neurogenic vasodilation of amphibian arterioles and pre-capillary sphincters. I. Light microscopy. Microvascular Res.3, 308–322 (1971)CrossRefGoogle Scholar
  21. Stone, C. A.: Hypotensive 4,5-dihydroxy-a-methyl-phenylethylamine derivatives. Chem. Abstr.61 6953 e. Belgian Patent No. 633, 963 (1964)Google Scholar
  22. Thoenen, H. Tranzer, J.-P. Chemical sympathectomy by selective destruction of adrenergic nerve endings with 6-hydroxydopamine. Naunyn-Schmiedebergs. Arch. Pharmak. exp. Path.261, 271–288 (1968)CrossRefGoogle Scholar
  23. Tranzer, J.-P., Thoenen, H.: An electron microscopic study of selective, acute degeneration of sympathetic nerve terminals after administration of 6-hydroxydopamine. Experientia (Basel)24, 155–156 (1968)Google Scholar
  24. Tranzer, J.-P., Thoenen, H.: Selective destruction of adrenergic nerve terminals by chemical analogues of 6-hydroxydopamine. Experientia (Basel)29, 314–315 (1973)Google Scholar
  25. Wagner, K.: Uncoupling of oxidative phosphorylation by 6-hydroxydopamine. In: 6-Hydroxydopamine and catecholamine neurons (T. Malmfors and H. Thoenen, eds.), p. 277–278. Amsterdam: North-Holland Publishing Co. 1971Google Scholar
  26. Wherli, P. A., Piggot, F., Fischer, U., Kaiser, A.: Oxydationsprodukte von 6-Hydroxydopamin. Helv. chim. Acta55, 3057–3061 (1972)Google Scholar

Copyright information

© Springer-Verlag 1973

Authors and Affiliations

  • George R. Siggins
    • 1
  • David S. Forman
    • 1
  1. 1.Laboratory of Neuropharmacology, N.I.M.H.St. Elizabeths HospitalWashington, D. C.U.S.A.

Personalised recommendations