Skip to main content
Log in

Increase in brain dopamine after axotomy or treatment with gammahydroxybutyric acid due to elimination of the nerve impulse flow

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

Both a unilateral, frontal section of the brain at the level of the caudal hypothalamus (hemisection) and systemic treatment with gammahydroxybutyric acid (GHBA, sodium form, 1.5 g/kg i.p.) increased the dopamine (DA) in the rat forebrain by about 70% in 1 h. Both procedures also markedly decelerated the α-methyltyrosine-induced DA disappearance. The brain noradrenaline was significantly lowered after the hemisection, but was not influenced by the treatment with GHBA given either alone or in combination with α-methyltyrosine.

Intrastriatal injections of 25% KCl did not change the normal DA content significantly but prevented the increase in DA observed after hemisection or treatment with GHBA, probably due to a depolarization of the DA nerve terminals. Such a treatment with KCl also rapidly released the DA accumulated after hemisection. These effects were not seen after 20% NaCl.

The same increase in forebrain DA, as produced by hemisection or treatment with GHBA, was also seen after injections of 25% KCl into the substantia nigra or injections of tetrodotoxin into the neostriatum.

To judge from the turning of rats, unilateral injections of 25% KCl into the neostriatum depolarized the cells in this area, whereas stimulation of the DA receptors hyperpolarized them.

The increases in brain DA described may be due to an inhibition of the nerve impulse flow to the DA nerve terminals.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Adrian, R. H.: The effect of internal and external potassium concentration on the membrane potential of frog muscle. J. Physiol. (Lond.) 133, 631–658 (1956).

    Google Scholar 

  • Aghajanian, G. K., Roth, R. H.: γ-Hydroxybutyrate-induced increase in brain dopamine: localization by fluorescence microscopy. J. Pharmacol. exp. Ther. 175, 131–138 (1970).

    Google Scholar 

  • Andén, N.-E., Bédard, P., Fuxe, K., Ungerstedt, U.: Early and selective increase in brain dopamine levels after axotomy. Experientia (Basle) 28, 300–301 (1972).

    Google Scholar 

  • Andén, N.-E., Corrodi, H., Dahlström, A., Fuxe, K., Hökfelt, T.: Effects of tyrosine hydroxylase inhibition on the amine levels of central monoamine neurons. Life Sci. 5, 561–568 (1966a).

    Google Scholar 

  • Andén, N.-E., Corrodi, H., Fuxe, K., Ungerstedt, U.: Importance of nervous impulse flow for the neuroleptic induced increase in amine turnover in central dopamine neurons. Europ. J. Pharmacol. 15, 193–199 (1971)

    Google Scholar 

  • Andén, N.-E., Dahlström, A., Fuxe, K., Larsson, K.: Functional role of the nigroneostriatal dopamine neurons. Acta pharmacol. (Kbh.) 24, 263–274 (1966b).

    Google Scholar 

  • Andén, N.-E., Magnusson, T., Stock, G.: Effects of drugs influencing monoamine mechanisms on the increase in brain dopamine produced by axotomy or treatment with gamma hydroxybutyric acid. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 363–372 (1973).

    Google Scholar 

  • Andén, N.-E., Rubenson, A., Fuxe, K., Hökfelt, T.: Evidence for dopamine receptor stimulation by apomorphine. J. Pharm. Pharmacol. 19, 627–629 (1967).

    Google Scholar 

  • Atack, C. V.: The determination of dopamine by a modification of the dihydroxyindole fluorimetric assay. Brit. J. Pharmacol. (in press).

  • Atack, C. V., Magnusson, T.: Individual elution of noradrenaline (together with adrenaline), dopamine, 5-hydroxytryptamine and histamine from a single, strong cation exchange column, by means of mineral acid-organic solvent mixtures. J. Pharm. Pharmacol. 22, 625–627 (1970).

    Google Scholar 

  • Bédard, P., Carlsson, A., Lindqvist, M.: Effect of a transverse cerebral hemisection on 5-hydroxytryptamine metabolism in the rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 272, 1–15 (1972).

    Google Scholar 

  • Bertler, Å., Carlsson, A., Rosengren, E.: A method for the fluorimetric determination of adrenaline and noradrenaline in tissues. Acta physiol. scand. 44, 273–292 (1958).

    Google Scholar 

  • Besson, M.-J., Cheramy, A., Feltz, P., Glowinski, J.: Dopamine: spontaneous and drug-induced release from the caudate nucleus in the cat. Brain Res. 32, 407–424 (1971).

    Google Scholar 

  • Bloom, F. E., Costa, E., Salmoiraghi, G. C.: Anesthesia and the responsiveness of individual neurons of the caudate nucleus of the cat to acetylcholine, norepinephrine and dopamine administered by microelectrophoresis. J. Pharmacol. exp. Ther. 150, 244–252 (1965).

    Google Scholar 

  • Carlsson, A., Lindqvist, M.: In vivo decarboxylation of α-methyl DOPA and α-methyl metatyrosine. Acta physiol. scand. 54, 87–94 (1962).

    Google Scholar 

  • Carlsson, A., Waldeck, B.: A fluorimetric method for the determination of dopamine (3-hydroxytyramine). Acta physiol. scand. 44, 293–298 (1958).

    Google Scholar 

  • Connor, J. D.: Caudate nucleus neurones: correlation of the effects of substantia nigra stimulation with iontophoretic dopamine. J. Physiol. (Lond.) 208, 691–703 (1970).

    Google Scholar 

  • Dahlström, A., Fuxe, K., Kernell, D., Sedvall, G.: Reduction of the monoamine stores in the terminals of bulbospinal neurons following stimulation in the medulla oblongata. Life Sci. 4, 1207–1212 (1965).

    Google Scholar 

  • Feltz, P., de Champlain, J.: Enhanced sensitivity of caudate neurones to microiontophoretic injections of dopamine in 6-hydroxydopamine treated cats. Brain Res. 43, 601–605 (1972).

    Google Scholar 

  • Gessa, G. L., Crabai, F., Vargiu, L., Spano, P. F.: Selective increase of brain dopamine induced by γ-hydroxybutyrate: study of the mechanism of action. J. Neurochem. 15, 377–381 (1968).

    Google Scholar 

  • Gessa, G. L., Vargiu, L., Crabai, F., Boero, G. C., Caboni, F., Camba, R.: Selective increase of brain dopamine induced by gamma-hydroxybutyrate. Life Sci. 5, 1921–1930 (1966).

    Google Scholar 

  • Giarman, N. J., Schmidt, K. F.: Some neurochemical aspects of the depressant action of γ-butyrolactone on the central nervous system. Brit. J. Pharmacol. 20, 563–568 (1963).

    Google Scholar 

  • Häggendal, J.: An improved method for fluorimetric determination of small amounts of adrenaline and noradrenaline in plasma and tissues. Acta physiol. scand. 59, 242–254 (1963).

    Google Scholar 

  • Hassler, R., Bak, I. J.: Unbalanced ratios of striatal dopamine and serotonin after experimental interruption of strionigral connections in rat. In: F. J. Gillingham, I. M. L. Donaldson: Third symposium on Parkinson's disease, pp. 29–37. Edinburgh-London: Livingstone 1969.

    Google Scholar 

  • Herz, A., Zieglgänsberger, W.: The influence of microelectrophoretically applied biogenic amines, cholinomimetics and procaine on synaptic excitation in the corpus striatum. Internal. J. Neuropharmacol. 7, 221–230 (1968).

    Google Scholar 

  • Hillman, H. H., McIlwain, H.: Membrane potentials in mammalian cerebral tissues in vitro: dependence on ionic environment. J. Physiol. (Lond.) 157, 263–278 (1961).

    Google Scholar 

  • Hutchins, D. A., Rayevsky, K. S., Sharman, D. F.: The effect of sodium γ-hydroxybutyrate on the metabolism of dopamine in the brain. Brit. J. Pharmacol. 46, 409–415 (1972).

    Google Scholar 

  • Kao, C. Y.: Tetrodotoxin, saxitoxin and their significance in the study of excitation phenomena. Pharmacol. Rev. 18, 997–1049 (1966).

    Google Scholar 

  • Kehr, W., Carlsson, A., Lindqvist, M., Magnusson, T., Atack, C.: Evidence for a receptor-mediated feedback control of striatal tyrosine hydroxylase activity. J. Pharm. Pharmacol. 24, 744–747 (1972).

    Google Scholar 

  • Keller, H. H., Bartholini, G., Pieri, L., Pletscher, A.: Effects of spreading depression on the turnover of cerebral dopamine. Europ. J. Pharmacol. 20, 287–290 (1972).

    Google Scholar 

  • Kirpekar, S. M., Wakade, A. R.: Release of noradrenaline from the cat spleen by potassium. J. Physiol. (Lond.) 94, 595–608 (1968).

    Google Scholar 

  • König, J. F. R., Klippel, R. A.: The rat brain. A stereotaxic atlas of the forebrain and lower parts of the brain stem. Baltimore: Williams and Wilkins 1963.

    Google Scholar 

  • Kuhar, M. J., Roth, R. H., Aghajanian, G. K.: Selective reduction of tryptophan hydroxylase activity in rat forebrain after midbrain raphe lesions. Brain Res. 35, 167–176 (1971).

    Google Scholar 

  • Liley, A. W.: The effects of presynaptic polarization on the spontaneous activity at the mammalian neuromuscular junction. J. Physiol. (Lond.) 134, 427–443 (1956).

    Google Scholar 

  • McLennan, H., York, D. H.: The action of dopamine on neurones of the caudate nucleus. J. Physiol. (Lond.) 189, 393–402 (1967).

    Google Scholar 

  • Pepeu, G., Mantegazzini, P.: Midbrain hemisection: effect on cortical acetylcholine in the cat. Science 145, 1069–1070 (1964).

    Google Scholar 

  • Roth, R. H., Suhr, Y.: Mechanism of the γ-hydroxybutyrate-induced increase in brain dopamine and its relationship to “sleep”. Biochem. Pharmacol. 19, 3001–3012 (1970).

    Google Scholar 

  • Stille, G., Sayers, A.: Effect of a striatal spreading depression on the pharmacogenic catatonia. Int. J. Neuropharmacol. 8, 181–189 (1969).

    Google Scholar 

  • Ungerstedt, U., Butcher, L. L., Butcher, S. G., Andén, N.-E., Fuxe, K.: Direct chemical stimulation of dopaminergic mechanisms in the neostriatum of the rat. Brain Res. 14, 461–471 (1969).

    Google Scholar 

  • Walters, J. R., Aghajanian, G. K., Roth, R. H.: Dopaminergic neurons: inhibition of firing by γ-hydroxybutyrate. In: Proc. Fifth Pharmacol. Congr., Abstract Vol., p. 246. San Francisco 1972.

  • Weiss, T., Fifková, E.: The effect of neocortical and caudatal spreading depression on “circling movements” induced from the caudata nucleus. Physiol. bohemoslov. 12, 332–338 (1963).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stock, G., Magnusson, T. & Andén, NE. Increase in brain dopamine after axotomy or treatment with gammahydroxybutyric acid due to elimination of the nerve impulse flow. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 347–361 (1973). https://doi.org/10.1007/BF00501479

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00501479

Key words

Navigation