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Psychopharmacology

, Volume 50, Issue 3, pp 225–229 | Cite as

Differential actions of dopamine agonists and antagonists on the γ-butyrolactone-induced increase in mouse brain dopamine

  • Gerald Gianutsos
  • John E. Thornburg
  • Kenneth E. Moore
Animal Studies

Abstract

γ-Butyrolactone (GBL) increased the dopamine concentration in the forebrain of the mouse. Apomorphine dose-dependently antagonized the GBL effect, while piribedil was less effective. Haloperidol prevented the antagonism of GBL by apomorphine but pimozide was ineffective in blocking apomorphine. After chronic treatment with haloperidol or pimozide, there was no alteration of the maximum GBL-induced increase in dopamine nor was there any significant change in the antagonism by apomorphine, although a trend toward increased sensitivity to apomorphine was noted in the group withdrawn from haloperidol. These results suggest that in the mouse, haloperidol is a more effective antagonist of presynaptic dopamine autoreceptors than pimozide, while apomorphine is a better presynaptic agonist than piribedil.

Key words

γ-Butyrolactone Haloperidol Pimozide Apomorphine Piribedil Dopamine 

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References

  1. Andén, N. E., Butcher, S. G., Corrodi, M., Fuxe, K., Ungerstedt, U.: Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Europ. J. Pharmacol 11, 303–314 (1970)Google Scholar
  2. Chang, C. C.: A sensitive method for spectrophotofluorometric assay of catecholamines. Int. J. Neuropharmacol. 3, 643–649 (1964)Google Scholar
  3. Corrodi, H., Farnebo, L. O., Fuxe, K., Hamberger, B., Ungerstedt, U.: E1495 and brain catecholamine mechanisms: Evidence for stimulation of dopamine receptors. Europ. J. Pharmacol. 20, 195–204 (1972)Google Scholar
  4. Gessa, G. L., Vargiu, L., Crabai, F., Bocro, G. C., Caboni, F., Camba, R.: Selective increase of brain dopamine induced by γ-hydroxybutyrate. Life Sci. 5, 1921–1930 (1966)Google Scholar
  5. Gianutsos, G., Drawbaugh, R. B., Hynes, M. D., Lal, H.: Behavioral evidence for dopamine supersensitivity after chronic haloperidol. Life Sci. 14, 887–898 (1974)Google Scholar
  6. Handforth, A., Sourkes, T. L.: Inhibition by dopamine agonists of dopamine accumulation following γ-hydroxybutyrate treatment. Europ. J. Pharmacol. 34, 311–319 (1975)Google Scholar
  7. 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
  8. Niemegeers, C. J. E.: Prediction of side effects. In: Neuroleptics, S. Fielding and H. Lal, eds., pp. 76–129. Mt. Kisco, New York: Futura 1974Google Scholar
  9. Roth, R. H., Walters, J. R., Aghajanian, G. K.: Effect of impulse flow on the release and synthesis of dopamine in the rat striatum. In: Frontiers in catecholamine research, E. Usdin and S. M. Snyder, eds., pp. 567–574. New York: Pergamon Press 1973Google Scholar
  10. Roth, R. H., Walters, J. R., Murrin, L. C., Morgenroth, V. M.: Dopamine neurons: Role of impulse flow and pre-synaptic receptors in the regulation of tyrosine hydroxylase. In: Preand postsynaptic receptors, E. Usdin and W. E. Bunney, eds., pp. 5–48. New York: Marcel Dekker 1975Google Scholar
  11. Spano, P. F., Tagliamonte, A., Tagliamonte, P., Gessa, G. L.: Stimulation of brain dopamine synthesis by γ-hydroxybutyrate. J. Neurochem. 18, 1831–1836 (1971)Google Scholar
  12. Tarsy, D., Baldessarini, R. J.: Behavioral supersensitivity to apomorphine following chronic treatment with drugs which interfere with the synaptic function of catecholamines. Neuropharmacology 13, 927–940 (1974)Google Scholar
  13. Thornburg, J. E., Moore, K. E.: Supersensitivity to dopaminergic agonists induced by haloperidol. In: Aminergic hypotheses of behavior: reality or cliche?, B. K. Bernard, ed., pp. 23–28. Rockville, Maryland: NIDA 1975Google Scholar
  14. Thornburg, J. E., Moore, K. E.: A comparison of effects of apomorphine and ET495 on locomotor activity and circling behavior in mice. Neuropharmacology 13, 189–197 (1974)Google Scholar
  15. von Voightlander, P. F., Losey, E. G., Triezenberg, H. J.: Increased sensitivity to dopaminergic agents after chronic neuroleptic treatment. J. Pharmacol. exp. Ther. 193, 88–94 (1975)Google Scholar
  16. Walters, J. R., Roth, R. H.: Dopaminergic neurons: Drug-induced antagonism of the increase in tyrosine hydroxylase activity produced by cessation of impulse flow. J. Pharmacol. exp. Ther. 191, 82–91 (1974)Google Scholar
  17. Walters, J. R., Roth, R. H.: Effect of γ-hydroxybutyrate on dopamine and dopamine metabolites in the rat striatum. Biochem. Pharmacol. 21, 2111–2121 (1972)Google Scholar
  18. Walters, J. R., Roth, R. H., Aghajanian, G. K.: Dopaminergic neurons: Similar biochemical and histochemical effects of γ-hydroxybutyrate and acute lesions of the nigro-neostriatal pathway. J. Pharmacol. exp. Ther. 186, 630–639 (1973)Google Scholar

Copyright information

© Springer-Verlag 1976

Authors and Affiliations

  • Gerald Gianutsos
    • 1
  • John E. Thornburg
    • 1
  • Kenneth E. Moore
    • 1
  1. 1.Department of PharmacologyMichigan State UniversityEast LansingU.S.A.

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