Suppression by dopamine-agonists of the ethanol-induced stimulation of locomotor activity and brain dopamine synthesis

  • Arvid Carlsson
  • Jörgen Engel
  • Ulf Strömbom
  • Torgny H. Svensson
  • Bertil Waldeck
Article
Received:

Summary

Ethanol, 2.2 g/kg was given intraperitoneally to mice, grouped 3 by 3, alone or together with either of the dopamine-receptor stimulating agents apomorphine, 2.5 mg/kg, or ET 495, 5 mg/kg. Control animals received saline injections. Locomotor activity was then recorded every 5 min for 60 min, starting 5–7 min after the injection. Apomorphine and ET 495, which had no marked effect on the locomotor activity, both inhibited the locomotor stimulation induced by ethanol. Other animals received ethanol, 4 g/kg, alone or together with either apomorphine or ET 495, and at various time intervals thereafter, 3H-labelled tyrosine. Control animals received 3H-tyrosine alone. The net yield of 3H-dopamine and 3H-noradrenaline in the brain as well as the specific activity of 3H-tyrosine in plasma 10 min after the 3H-tyrosine injection were measured. Apomorphine and ET 495, 2.5 and 5 mg/kg, respectively, did not change the net yield of 3H-dopamine and 3H-noradrenaline. However, both of them inhibited the ethanol-induced increase in net yield of 3H-dopamine. This effect of apomorphine and ET 495 could not be ascribed to changes in the specific activity of 3H-tyrosine in the plasma. Apomorphine had no effect on the blood level of ethanol as measured 1 h after the administration of ethanol. The possibility that the inhibitory effects of the dopamine-agonists on the ethanol-induced stimulation of the dopamine synthesis and locomotor activity may be mediated by stimulation of presynaptic, inhibitory receptors is discussed.

Key words

Ethanol Apomorphine ET 495 Locomotor Activity Dopamine Receptors Dopamine Synthesis 
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aghajanian, G. K., Bunney, B. S.: Central dopaminergic neurons: Neurophysiological identification and responses to drugs: In: Frontiers in Catecholamine Research. E. Usdin and S. Snyder, Eds. Elmford-New York: Pergamon Press 1973aGoogle Scholar
  2. Aghajanian, G. K., Bunney, B. S.: Pre- and postsynaptic feedback mechanisms in central dopaminergic neurons. In: Neurotransmitters and Brain Function. Neuroscience Symposium. Toronto, Nov. 2 and 3, 1973bGoogle Scholar
  3. Ahlenius, S., Brown, R., Engel, J., Svensson, T. H., Waldeck, B.: Antagonism by nialamide of the ethanol-induced locomotor stimulation in mice. J. Neural. Transmission. (in press) (1974)Google Scholar
  4. Ahlenius, S., Carlsson, A., Engel, J., Svensson, T. H., Södersten, P.: Antagonism by alpha methyltyrosine of the ethanol-induced stimulation and euphoria in man. Clin. Pharmacol. Ther. 14, 586–591 (1973)Google Scholar
  5. 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
  6. Carlsson, A., Davis, J. N., Kehr, W., Lindqvist, M., Atack, C. V.: Simultaneous measurement of tyrosine and tryptophan hydroxylase activities in brain in vivo using an inhibitor of the aromatic amino acid decarboxylase. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 153–168 (1972a)Google Scholar
  7. Carlsson, A., Engel, J., Svensson, T. H.: Inhibition of ethanol-induced excitation in mice and rats by α-methyl-π-tyrosine. Psychopharmacologia (Berl.) 26, 307–312 (1972b)Google Scholar
  8. Carlsson, A., Lindqvist, M.: Effect of ethanol on the hydroxylation of tyrosine and tryptophan in rat brain in vivo. J. Pharm. Pharmacol. 25 437–440 (1973)Google Scholar
  9. Carlsson, A., Lindqvist, M., Magnusson, T.: On the biochemistry and possible functions of dopamine and noradrenaline in brain. In: Ciba Symposium on Adrenergic Mechanisms, pp. 432–439. J. R. Vane, G. E. Wolstenholme, and M. O'Connor, Eds. London: J. and A. Churchill Ltd. 1960Google Scholar
  10. Carlsson, A., Magnusson, T., Svensson, T. H., Waldeck, B.: Effect of ethanol on the metabolism of brain catecholamines. Psychopharmacologia (Berl.) 30, 27–36 (1973)Google Scholar
  11. Corrodi, H., Farnebo, L. O., Fuxe, K., Hamberger, B., Ungerstedt, U.: ET 495 and brain catecholamine mechanisms: Evidence for stimulation of dopamine receptors. Europ. J. Pharmacol. 20, 195–204 (1972)Google Scholar
  12. Corrodi, H., Fuxe, K., Hökfelt, T.: The effect of ethanol on the activity of the catecholamine neurons in the rat brain. J. Pharm. Pharmacol. 18, 821–823 (1966)Google Scholar
  13. Corrodi, H., Fuxe, K., Ungerstedt, U.: Evidence for a new type of dopamine receptor stimulating agent. J. Pharm. Pharmacol. 23, 989–991 (1971)Google Scholar
  14. Dent, J. Y.: Apomorphine in the treatment of anxiety states with especial reference to alcoholism. Brit. J. Inebr. 32, 65–88 (1934)Google Scholar
  15. Engel, J., Strömbom, U., Svensson, T. H., Waldeck, B.: Suppression by α-methyl-tyrosine of the ethanol-induced locomotor stimulation: Partial reversal by l-Dopa. Psychopharmacologia (Berl.) (in press) (1974)Google Scholar
  16. Ernst, A. M.: Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia (Berl.) 10, 316–323 (1967)Google Scholar
  17. Goldstein, M., Freedman, L. S., Backstrom, T.: The inhibition of catecholamine biosynthesis by apomorphine. J. Pharm. Pharmacol. 22, 715–717 (1970)Google Scholar
  18. Kehr, W., Carlsson, A., Lindqvist, M., Magnusson, T., Atack, C.: Evidence for a receptor-mediated feedback control of strial tyrosine hydroxylase activity. J. Pharm. Pharmacol. 24, 744–747 (1972)Google Scholar
  19. Lewander, T., Jonsson, J.: Isolation and determination of free endogenous and radio-active tyrosine in studies on catecholamine synthesis in the rat brain. Life Sci. 7, 387–394 (1968)Google Scholar
  20. Neff, N. H., Costa, E.: Antidepressant drugs. Proceedings of the first international symposium, pp. 28–34. S. Garattini and M. N. Dukes, Eds. Amsterdam: Excerpta Medica Foundation, International Congress Series 1966Google Scholar
  21. Persson, T.: Drug induced changes in 3H-catecholamine accumulation after 3H-tyrosine. Acta pharmacol. (Kbh.) 28, 378–390 (1970)Google Scholar
  22. Persson, T., Waldeck, B.: The use of 3H-Dopa for studing cerebral catecholamine metabolism. Acta pharmacol. (Kbh.) 26, 363–372 (1968)Google Scholar
  23. Read, G. W., Cutting, W., Furst, A.: Comparison of excited phases after sedatives and tranquilizers. Psychopharmacologia (Berl.) 1 346–350 (1960)Google Scholar
  24. Reynolds, G. S., Sommers, P. van: Effects of ethyl alcohol on avoidance behaviour. Science 132, 42–43 (1960)Google Scholar
  25. Schlatter, E. K. E., Lal, S.: Treatment of alcoholism with Dent's oral apomorphine method. Quart, J. Stud. Alcohol. 33, 430–436 (1972)Google Scholar
  26. Sunshine, I., Nenad, R.: A modification of Winnik's method for the rapid determination of ethyl alcohol in biological fluids. Analyt. Chem. 25, 653–655 (1953)Google Scholar
  27. Waalkes, T. P., Udenfriend, S.: A fluorimetric method for the estimation of tyrosine in plasma and tissue. J. Lab. clin. Med. 50, 733–736 (1957)Google Scholar
  28. Waldeck, B.: Ethanol and caffeine: A complex interaction with respect to locomotor activity and central catecholamines. Psychopharmacologia (Berl.) 36, 209–220 (1974)Google Scholar
  29. Weiss, B., Laties, B. G.: Effects of amphetamine, chlorpromazine, pentobarbital, and ethanol on operant response duration. J. Pharmacol. exp. Ther. 144, 17–23 (1964)Google Scholar

Copyright information

© Springer-Verlag 1974

Authors and Affiliations

  • Arvid Carlsson
    • 1
  • Jörgen Engel
    • 1
  • Ulf Strömbom
    • 1
  • Torgny H. Svensson
    • 1
  • Bertil Waldeck
    • 1
  1. 1.Department of PharmacologyUniversity of GöteborgGöteborgSweden

Personalised recommendations