Dopamine Release and Metabolism in Awake Rats after Systemic Neuroleptics as Studied by Brain Dialysis

  • G. di Chiara
  • A. Imperato
Part of the Satellite Symposia of the IUPHAR 9th International Congress of Pharmacology book series (SSNIC)


Drugs which block central dopamine (DA)-receptors (neuroleptics) are known to stimulate the synthesis and the metabolism of DA (Carlsson and Lindquist, 1963; Javoy et al., 1970; Andén et al., 1971) and the firing activity of DA-neurons (Bunney et al., 1973). Such effects have been taken as evidence for the existence of feedback or autoregulatory mechanism in the dopaminergic system (Carlsson and Lindquist, 1963; Carlsson, 1975; Bunney and Aghajanian, 1976). According to this hypothesis the functional activity of the DA-neurons is negatively regulated by the amount of DA released from DA-terminals or dendrites (Bjorklund and Lindvall, 1975; Geffen et al., 1976; Korf et al., 1976; Nieoullon et al., 1977) onto DA-receptors located either post-synaptically in the caudate (Carlsson and Lindquist, 1963; Bunney and Aghajanian, 1976) or on non-dopaminergic terminals of the substantia nigra (Phillipson and Horn, 1976; Spano et al., 1976; Spano et al., 1977) or on the DA-neurons themselves, either in the caudate (terminal auto-receptors) (Carlsson, 1975), or in the nigra (nigral auto-receptors) (Aghajanian and Bunney, 1977).


Tyrosine Hydroxylase Dopamine Receptor Dopamine Release Firing Activity Dialysis Tube 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aghajanian, G.K. and Bunney, B.S. (1977). Dopamine’s autoreceptors: Pharmacological characterization by microiontophoretic single cell recording studies. Naunyn-Schmiedeberg’s Arch. Pharmacol., 297, 1–7.CrossRefGoogle Scholar
  2. Andén, N.E., Corrodi, H., Fuxe, K., Ungerstedt, U. (1971). Importance of nervous impulse flow the neuroleptic induced increase in amine turnover in central dopamine neurons. Europ. J. Pharmacol., 15, 193–199.CrossRefGoogle Scholar
  3. Arbilla, S. and Langer, S.Z. (1981). Stereoselectively of presynaptic autoreceptors modulating dopamine release. Europ. J. Pharmacol., 76, 345–351.CrossRefGoogle Scholar
  4. Björklund, A. and Lindvall, O. (1975). Dopamine in dendrites of substantia nigra neurons: Suggestions for a role in dendritic terminals. Brain Res., 83, 531–537.PubMedCrossRefGoogle Scholar
  5. Bunney, B.S., Walters, J.R., Roth, R.H. and Aghajanian, G.K. (1973). Dopaminergic neurons: Effect of antipsychotic drugs and amphetamine on single cell activity. J. Pharmacol. Exp. Ther., 195, 560–571.Google Scholar
  6. Bunney, B.S. and Aghajanian, G.K. (1976). d-Amphetamine-induced inhibition of central dopaminergic neurons: Mediation by a striato-nigral feedback pathway. Science, 192, 391–393.Google Scholar
  7. Carlsson, A., Lindquist, M. (1963). Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normethanephrine in mouse brain. Acta Pharmacol., 20, 140–144.CrossRefGoogle Scholar
  8. Carlsson, A. (1975). Receptor-mediated control of dopamine metabolism. In Pre- and Postsynaptic Receptors. (eds. E. Usdin and W.E. Bunney, Jr.). Marcel Dekker, New York.Google Scholar
  9. Di Chiara, G., Porceddu, M.L., Fratta, W. and Gessa, G.L. (1977). Postsynaptic receptors are not essential for dopaminergic feedback regulation. Nature, 267, 270.PubMedCrossRefGoogle Scholar
  10. Di Chiara, G., Porceddu, M.L., Vargiu, L., Argiolas, A. and Gessa, G.L. (1976). Evidence for dopamine receptors mediating sedation in the mouse brain. Nature, 264, 564–567.PubMedCrossRefGoogle Scholar
  11. Di Chiara, G., Onali, P.L., Tissari, A.H., Porceddu, M.L., Morelli, M. and Gessa, G.L. (1978). Destruction of post-synaptic dopamine receptors prevents neuroleptic-induced activation of striatal tyrosine hydroxylase but not dopamine synthesis stimulation. Life Sci., 23, 691–696.PubMedCrossRefGoogle Scholar
  12. Enna, S.J., Bennett, J.P., Burt, D.R., Creese, I. and Snyder, S.H. (1976). Stereospecificity of interaction of neuroleptic drugs with neurotransmitters and correlation with clinical potency. Nature, 263, 338–341.PubMedCrossRefGoogle Scholar
  13. Farnebo, L.O., Hamberger, B. (1971). Drug-induced changes in the release of 3H-monoamines from field stimulated rat brain slices. Acta Physiol. Scand., 371, 35–44.CrossRefGoogle Scholar
  14. Geffen, L.B., Jessel, T.M., Cuello, A.C. and Iversen, L.L. (1976). Release of dopamine from dendrites in rat substantia nigra. Nature, 260, 258–260.PubMedCrossRefGoogle Scholar
  15. Imperato, A. and Di Chiara, G. (1984). Trans-striatal dialysis coupled to reverse-phase high performance liquid chromatography with electrochemical detection: A new method for the study of the in vivo release of endogenous dopamine and metabolites. J. Neurosci., 4, 966–984.PubMedGoogle Scholar
  16. Imperato, A. and Di Chiara, G. (1984). Dopamine-release and metabolism in awake rats after systemic neuroleptics as studied by trans-striatal dialysis. J. Neurosci., (in press).Google Scholar
  17. Jackisch, R., Zumstein, A., Hertting, G. and Starke, K. (1980). Interneurones are probably not involved in the presynaptic dopaminergic control of dopamine release in the rabbit caudate nucleus. Naunyn-Schmiedeberg’s Arch. Pharmacol., 314, 129.CrossRefGoogle Scholar
  18. Javoy, F., Hamon, M., Glowinski, J. (1970). Disposition of newly synthesized amines in cell bodies and terminals of central catecholaminergic neurons. I. Effects of amphetamine and thioproperazine on the metabolism of catecholamines in the caudate nucleus, the substantia nigra and the ventromedial nucleus of the hypothalamus. Europ. J. Pharmacol., 10, 178–188.CrossRefGoogle Scholar
  19. Kamal, L., Arbilla, S. and Langer, S.Z. (1981). Presynaptic modulation of the release of dopamine from the rabbit caudate nucleus: Differences between electrical stimulation, amphetamine and tyramine. J. Pharmacol. Exp. Ther., 216, 592.PubMedGoogle Scholar
  20. Kehr, W., Carlsson, A., Lindquist, M., Magnusson, T., Atack, C.V. (1972). Evidence for a receptor mediated feedback control of striatal tyrosine hydroxylase activity. J. Pharm. Pharmacol., 24, 744–747.PubMedCrossRefGoogle Scholar
  21. Kondo, Y. and Iwatsubo, K. (1980). Diminished responses of nigral dopaminergic neurons to haloperidol and morphine following lesions in the striatum. Brain Res., 181, 237.PubMedCrossRefGoogle Scholar
  22. König, J.F.R. and Klippel, R.A. (1970). The rat brain: A stereotaxic Atlas.Google Scholar
  23. Korf, J., Zielman, M. and Westerink, B.H.C. (1976). Dopamine release in substantia nigra. Nature, 260, 257–258.PubMedCrossRefGoogle Scholar
  24. Mereu, G.P., Casu, M. and Gessa, G.L. (1983). (-)-Sulpiride activates the firing rate and tyrosine hydroxylase activity of dopaminergic neurons in unanaesthetized rats. Brain Res., 264, 105–110.PubMedCrossRefGoogle Scholar
  25. Miller, R.J., Horn, A.S. and Iversen, L.L. (1974). The action of neuroleptic drugs on dopamine-stimulated adenosine cyclic 3’,5’-monophosphate production in neostriatum and limbic forebrain. Mol. Pharmacol., 10, 759–766.Google Scholar
  26. Nieoullon, A., Chéramy, A. and Glowinski, J. (1977). Release of dopamine in vivo from cat substantia nigra. Nature, 266, 375–377.PubMedCrossRefGoogle Scholar
  27. Nieoullon, A., Chéramy, A., Leviel, V. and Glowinski, J. (1979). Effects of the unilateral nigral application of dopaminergic drugs on the in vivo release of dopamine in the two caudate nuclei of the cat. Europ. J. Pharmacol., 53, 289–296.CrossRefGoogle Scholar
  28. Nyback, H., Sedvall, G. (1968). Effect of chlorpromazine on accumulation and disappearance of catecholamines formed from tyrosine-14C in brain. J. Pharmacol. Exp. Ther., 162, 294–301.PubMedGoogle Scholar
  29. Phillipson, O.T. and Horn, A.S. (1976). Substantia nigra of the rat contains a dopamine-sensitive adenylate cyclase. Nature, 261, 418–420.PubMedCrossRefGoogle Scholar
  30. Raiteri, M., Cervoni, A.M., Del Carmine, R., Levi, G. (1979). Lack of presynaptic autoreceptors controlling dopamine release in striatal synaptosomes. In Presynaptic Receptors. (eds. S.Z. Langer, K. Starke, M.L. Dubocovich). Pergamon Press, New York.Google Scholar
  31. Reimann, W., Zumstein, A., Jackisch, R., Starke, K. and Hertting, G. (1979). Effect of extracellular dopamine on the release of dopamine in the rabbit caudate nucleus: Evidence for a dopaminergic feedback inhibition. Naunyn-Schmiedeberg’s Arch. Pharmacol., 306, 53–60.CrossRefGoogle Scholar
  32. Roos, B.E. (1965). Effect of certain tranquillizers on the level of homovanillic acid in the corpus striatum. J. Pharm. Pharmacol., 17, 820–821.PubMedCrossRefGoogle Scholar
  33. Sharman, D.F. (1966). Changes in the metabolism of 3,4-dihydroxyphenylethylamine (dopamine) in the striatum of the mouse induced by drugs. Brit. J. Pharmacol., 28, 153–163.PubMedPubMedCentralGoogle Scholar
  34. Spano, P.F., Di Chiara, G., Tonon, G. and Trabucchi, M. (1976). A dopamine-stimulated adenylate cyclase in rat substantia nigra. J. Neurochem., 27, 1565–1568.PubMedCrossRefGoogle Scholar
  35. Spano, P.F., Trabucchi, M. and Di Chiara, G. (1977). Localization of nigral dopamine-sensitive adenylate cyclase on neurons originating from corpus striatum. Science, 196, 1343–1345.PubMedCrossRefGoogle Scholar
  36. Spano, P.F., Stefanini, E., Trabucchi, M. and Fresia, P. (1979). Stereospecific interaction of sulpiride on striatal and nonstriatal dopamine receptors. In Sulpiride and Other Benzamides. (eds. P.F. Spano, M. Trabucchi, G.U. Corsini and G.L. Gessa). Italian Brain Res. Found. Press, Milan.Google Scholar
  37. Stadler, H., Gadea Ciria, M. and Bartholini, G. (1975). “In vivo” release of endogenous neurotransmitters in cat limbic regions: Effect of chlorpromazine and of electrical stimulation. Naunyn-Schmiedeberg’s Arch. Pharmacol., 288, 1–6.Google Scholar
  38. Starke, K., Reimann, W., Zumstein, A., Hertting, G. (1978). Effect of dopamine receptor agonists and antagonists on release of dopamine in the rabbit caudate nucleus in vitro. Naunyn-Schmiedeberg’s Arch. Pharmacol., 305, 27–36.CrossRefGoogle Scholar
  39. Trabucchi, M., Longoni, R., Fresia, P. and Spano, P.F. (1976). Sulpiride: A study of the effects on dopamine receptors in rat neostriatum and limbic forebrain. Life Science, 17, 1551–1556.CrossRefGoogle Scholar
  40. Walters, J.R., Roth, R.H. and Aghajanian, G.K. (1973). Dopaminergic neurons: similar biochemical and histochemical effects of y-hydroxybutyrate and acute lesions of the nigro-neostriatal pathway. J. Pharmacol. Exp. Ther., 186, 630–639.PubMedGoogle Scholar
  41. Westfall, T.C., Besson, M.J., Giorguieff, M.F., Glowinski, J. (1976). The role of presynaptic receptors in the release and synthesis of 3H-dopamine by slices of rat striatum. Naunyn-Schmiedeberg’s Arch. Pharmacol., 292, 279–287.CrossRefGoogle Scholar
  42. Zivkovic, B., Guidotti, A. (1974). Changes of kinetic constant of striatal tyrosine hydroxylase elicited by neuroleptics that impair the function of dopamine receptors. Brain Res., 79, 505–509.PubMedCrossRefGoogle Scholar
  43. Zivkovic, B., Guidotti, A. and Costa, E. (1975). The regulation of striatal tyrosine hydroxylase: Effects of gammahydroxybutyric acid and haloperidol. Naunyn-Schmiedeberg’s Arch. Pharmacol., 291, 193–200.CrossRefGoogle Scholar

Copyright information

© The Contributors 1986

Authors and Affiliations

  • G. di Chiara
  • A. Imperato

There are no affiliations available

Personalised recommendations