Skip to main content
Log in

Effects of drugs influencing monoamine mechanisms on the increase in brain dopamine produced by axotomy or treatment with gammahydroxybutyric acid

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

Summary

The influence of blockade or stimulation of dopamine (DA) receptors on the selective increase in brain DA seen after axotomy or injection of gammahydroxybutyric acid (sodium form, 1.5 g/kg i.p.) was studied in rats. The increases were not changed after blockade of the DA receptors by haloperidol but were slightly reduced after stimulation of these receptors by apomorphine. Since pretreatment with haloperidol counteracted this effect of apomorphine, a diminished stimulation of DA receptors may partially be responsible for the increase in brain DA seen when the nerve impulse flow has been blocked in the DA neurones by axotomy or treatment with gammahydroxybutyric acid. The NA content was usually somewhat lowered on the lesioned side and this reduction was not changed after treatment with haloperidol, apomorphine or amphetamine.

The increase in brain DA usually observed after axotomy was not found when the rats were also treated with reserpine and nialamide. This effect indicates that the negative feed-back of cytoplasmic DA on the DA synthesis operates also in the absence of nerve impulses.

Injection of amphetamine before or after axotomy or treatment with gammahydroxybytyric acid markedly inhibited the increase in brain DA, probably due to release of newly synthesized DA.

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

  • Alousi, A., Weiner, N.: The regulation of norepinephrine synthesis in sympathetic nerves: effect of nerve stimulation, cocaine, and catecholamine-releasing agents. Proc. nat. Acad. Sci. (Wash.) 56, 1491–1496 (1966).

    Google Scholar 

  • Andén, N.-E.: Effects of amphetamine and some other drugs on central catecholamine mechanisms. In: E. Costa and S. Garattini: Amphetamines and related compounds, pp. 447–462. New York: Raven Press 1970.

    Google Scholar 

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

    Google Scholar 

  • Andén, N.-E., Carlsson, A., Häggendal, J.: Adrenergic mechanisms. Ann. Rev. Pharmacol. 9, 119–134 (1969).

    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 (1966).

    Google Scholar 

  • Andén, N.-E., Magnusson, T.: Influences of drugs on the increases in brain dopamine produced by axotomy or gammahydroxybutyric acid. Acta pharmacol. (Kbh.) 31, Suppl. I, 27 (1972).

    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 

  • Carlsson, A.: Amphetamine and brain catecholamines. In: E. Costa and S. Garattini: Amphetamines and related compounds, pp. 289–300. New York: Raven Press 1970.

    Google Scholar 

  • Carlsson, A., Kehr, W., Lindqvist, M., Magnusson, T., Atack, C. V.: Regulation of monoamine metabolism in the central nervous system. Pharmacol. Rev. 24, 371–384 (1972).

    Google Scholar 

  • Carlsson, A., Lindqvist, M., Magnusson, T.: On the biochemistry and possible functions of dopamine and noradrenaline in brain. In: J. R. Vane, G. E. W. Wolstenholme, and M. O'Connor: Adrenergic mechanisms, pp. 432–439. London: Churchill 1960.

    Google Scholar 

  • Ernst, A. M.: Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia (Berl.) 10, 316–323 (1967).

    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 

  • Goldstein, M., Freedman, L. S., Backstrom, T.: The inhibition of catecholamine biosynthesis by apomorphine. J. Pharm. Pharmacol. 22, 715–717 (1970).

    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 

  • Javoy, F., Agid, Y., Bouvet, D., Glowinski, J.: Feedback control of dopamine synthesis in dopaminergic terminals of the rat striatum. J. Pharmacol. exp. Ther. 182, 454–463 (1972).

    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 

  • Neff, N. H., Costa, E.: Application of steady-state kinetics to the study of catecholamine turnover after monoamine oxidase inhibition or reserpine administration. J. Pharmacol. exp. Ther. 160, 40–47 (1968).

    Google Scholar 

  • Spector, S., Gordon, R., Sjoerdsma, A., Udenfriend, S.: End-product inhibition of tyrosine hydroxylase as a possible mechanism for regulation of norepinephrine synthesis. Molec. Pharmacol. 3, 549–555 (1967).

    Google Scholar 

  • Stock, G., Magnusson, T., Andén, N.-E.: 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).

    Google Scholar 

  • Sulser, F., Sanders-Bush, E.: Effect of drugs on amines in the CNS. Ann. Rev. Pharmacol. 11, 109–230 (1971).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Andén, NE., Magnusson, T. & Stock, G. Effects of drugs influencing monoamine mechanisms on the increase in brain dopamine produced by axotomy or treatment with gammahydroxybutyric acid. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 363–372 (1973). https://doi.org/10.1007/BF00501480

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00501480

Key words

Navigation