Skip to main content
SpringerLink
Log in

Histopathological changes associated with the intracerebral injection of 6-hydroxydopamine (6-OHDA) and peroxide (H2O2) in the cat and the rat

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

Several factors must be taken into consideration in order to establish whether or not 6-hydroxydopamine (6-OHDA) introduced in the CNS more or less selectively destroys monoaminergic and, more especially, catecholaminergic structures. These include an assessment of all elements possibly damaged following different sites of injection in various species, a comparison with the effects of known neurotoxic agents, the degree of diffusion and/or of dilution of the substance used, the assessment of associated behavioral, neurochemical and morphological changes in the light of the known topography of brain nervous structures etc. A comparison of the effects of 6-OHDA and of peroxide (H2O2) introduced in the CNS suggests that both agents produced similar morphological changes in various sites of the brains of cats and rats. In the light of various data in the literature and of the results reported in this study it appears that 6-OHDA which may be used to induce a focal lesion cannot be regarded as a specific neurotoxic agent.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Agid, Y., Javoy, F., Glowinski, J., Bovet, D., Sotelo, C.: Injections of 6-hydroxydopamine into the substantia nigra of the rat. II. Diffusion and specificity. Brain Res.58, 291–301 (1973).

    Google Scholar 

  • Aunis, D., Miras-Portugal, M. T., Mandel, P.: Inhibition of adrenal Dopamine-B-hydroxylase by 6-hydroxydopamine. Biochem. Pharmacol.22, 2581–2589 (1973).

    Google Scholar 

  • Breese, G. R., Traylor, T. D.: Developmental characteristics of brain catecholamines and tyrosine hydroxylase in the rat: effects of 6-hydroxydopamine. Br. J. Pharmacol.44, 210–222 (1972).

    Google Scholar 

  • Butcher, L. L., Eastgate, S. M., Hodge, G. K.: Evidence that punctate intracerebral administration of 6-hydroxydopamine fails to produce selective neuronal degeneration: Comparison with copper sulfate and factors governing the department of fluids injected into brain. Naunyn-Schmiedeberg's Arch. Pharmacol.285, 31–70 (1974).

    Google Scholar 

  • Cohen, G., Hochstein, P.: Glutathione peroxidase: the primary agent for the elemination of hydrogen peroxide in erythrocytes. Biochem.2, 1420 to 1428 (1963).

    Google Scholar 

  • Fibiger, H. C., Lonsbury, B., Cooper, H. P.: Early behavioural effects of intraventricular administration of 6-hydroxydopamine in rat. Nature New Biology236, 209–211 (1972 a).

    Google Scholar 

  • Fibiger, H.C., Pudritz, R.E., McGeer, P.L., McGeer, E.G.: Axonal transport in nigro-striatal and nigro-thalamic neurons: effects of medial forebrain bundle lesions and 6-hydroxydopamine. J. Neurochem.19, 1697–1708 (1972 b).

    Google Scholar 

  • Flohe, L., Brand, I.: Kinetics of glutathione peroxidase. Biochim. biophys. Acta191, 541–549 (1969).

    Google Scholar 

  • Heikkila, R., Cohen, G.: Inhibition of biogenic amine uptake by hydrogen peroxide: A mechanism for toxic effects of 6-hydroxydopamine. Science172, 1257–1258 (1971).

    Google Scholar 

  • Heikkila, R., Cohen, G.: Further studies on the generation of hydrogen peroxide by 6-OHDA. Molecular Pharmacol.8, 241–248 (1972).

    Google Scholar 

  • Heikkila, R., Cohen, G.: 6-Hydroxydopamine: Evidence for Superoxide radical as an oxidative intermediate. Science181, 456–458 (1973).

    Google Scholar 

  • Kaplanski, J., Nyakas, C., van Delft, A. M. L., Smelik, P. G.: Effect of central early postnatal 6-hydroxydopamine administration on brain catecholamines and pituitary-adrenal function in adulthood. Neuroendocrinology13, 123–217 (1973/74).

    Google Scholar 

  • Malmfors, T., Sachs, Ch.: Degeneration of adrenergic nerves produced by 6-hydroxydopamine. Europ. J. Pharmacol.3, 89–92 (1968).

    Google Scholar 

  • Poirier, L. J., Langelier, P., Roberge, A. G., Boucher, R., Kitsikis, A.: Nonspecific histopathological changes induced by the intracerebral injection of 6-hydroxydopamine (6-OHDA). J. neurol. Sci.16, 401–416 (1972).

    Google Scholar 

  • Roberge, A. G., Poirier, L. J.: Brain Dopa/5-HTP decarboxylase activity after the chronic administration of L-Dopa or 5-hydroxy-L-tryptophan in normal and lesioned cats. Brain Res.76, 401–412 (1974).

    Google Scholar 

  • Smith, R. D., Barrett, R., Breese, G. R.: Growth and behavioral changes in developing rats treated intracisternally with 6-hydroxydopamine: evidence for involvement of brain dopamme. J. Pharmacol. exp. Ther.185, 609–619 (1973).

    Google Scholar 

  • Sotelo, C., Javoy, F., Agid, Y., Glowinski, J.: Injection of 6-hydroxydopamine in the substantia nigra of the rat. I. Morphology study. Brain Res.58, 269–290 (1973).

    Google Scholar 

  • Tranzer, J. P., Thoenen, H.: Ultramorphologische Veränderungen der sympathischen Nervendigungen der Katze nach Vorbehandlung mit 5- und 6-Hydroxydopamine. Arch. Pharmakol, exptl. Path.257, 343–344 (1967).

    Google Scholar 

  • Tranzer, J. P., Thoenen, H.: An electron microscopic study of selective, acute degeneration of sympathetic nerve terminals after administration of 6-hydroxydopamine. Experientia24, 155–156 (1968).

    Google Scholar 

  • Ungerstedt, U.: 6-Hydroxydopamine-induced degeneration of central monoamine neurons. Europ. J. Pharmacol.5, 107–110 (1968).

    Google Scholar 

  • Ungerstedt, U.: Histochemical studies on the effect of intracerebral and intraventricular injections of 6-hydroxydopamine on monoamine neurons in the rat brain. In: 6-Hydroxydopamme lesions of the nigrostriatal dopamine system (Malmfors, T., Thoenen, H., eds.), pp. 101 to 127. Amsterdam: North-Holland. 1971.

    Google Scholar 

  • Ungerstedt, U., Arbuthnott, G.: Quantitative recording of rotational behaviour in rats after 6-hydroxydopamine lesions of the nigrostriatal dopamine system. Brain Res.24, 485–493 (1970).

    Google Scholar 

  • Uretsky, N. J., Iversen, L. L.: Effects of 6-hydroxydopamine on noradrenaline containing neurons in the rat brain. Nature (London)221, 557–559 (1969).

    Google Scholar 

  • Uretsky, N. J., Iversen, L. L.: Effects of 6-hydroxydopamine on catechol amine containing neurones in the rat brain. J. Neurochem.17, 269–278 (1970).

    Google Scholar 

  • Voigtlander, P. F. von, Moore, K. E.: Turning behavior of mice with unilateral 6-hydroxydopamine lesions in the striatum: effects of apomorphine, L-Dopa, amantadine, amphetamine and other psychomotor stimulants. Neuropharmcol.12, 451–462 (1973).

    Google Scholar 

  • Ziegler, H., Del Basso, P., Longo, V. G.: Influence of 6-hydroxydopamine and ofα-methyl-p-tyrosine on the effects of some centrally acting agents. Physiol. and Behavior.8, 391–396 (1972).

    Google Scholar 

  • Zigmond, J., Strieker, M.: Deficits in feeding behavior after intraventricular injection of 6-hydroxydopamine in rats. Science177, 1211–1214 (1972).

    Google Scholar 

Download references

Author information

Author notes

  1. L. J. Poirier

    Present address: Laboratoires de Neurobiologie, Faculté de Médecine, Université Laval, Quebec, Canada

Authors and Affiliations

    Authors
    1. L. J. Poirier
      View author publications

      You can also search for this author in PubMed Google Scholar

    Rights and permissions

    Reprints and permissions

    About this article

    Cite this article

    Poirier, L.J. Histopathological changes associated with the intracerebral injection of 6-hydroxydopamine (6-OHDA) and peroxide (H2O2) in the cat and the rat. J. Neural Transmission 37, 209–218 (1975). https://doi.org/10.1007/BF01670129

    Download citation

    • Received:

    • Issue Date:

    • DOI: https://doi.org/10.1007/BF01670129

    Keywords

    Search

    Navigation