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Dopamine “Autoreceptors”: Pharmacological characterization by microiontophoretic single cell recording studies

  • G. K. Aghajanian
  • B. S. Bunney
Article

Summary

The effects on the firing of single dopamine (DA) neurons in the substantia nigra (and adjacent ventral tegmental area) of a representative group of catecholamine agonists and antagonists were studied in rats using single cell recording and microiontophoretic techniques. Microiontophoretic application of DA or the DA agonist apomorphine depressed the firing of these cells; the DA antagonist trifluoperazine blocked this effect. However, the α-agonist clonidine had no depressant effect and the β-agonist isoproteronol had only a weak depressant action on DA neurons. Furthermore, the α-antagonist piperoxane and the β-antagonist sotolol were completely ineffective in blocking the depressant effects of DA. These results show that DA-sensitive receptors on the soma of DA neurons are pharmacologically distinct from α or β adrenoreceptors. Because of their location and selective responsiveness to DA agonists, the catecholamine receptors on the soma of DA neurons appear best classified as DA “autoreceptors”.

Key words

Autoreceptor Adrenoceptor Dopaminergic Microiontophoretic Substantia nigra 

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References

  1. Aghajanian, G. K., Bunney, B. S.: Central dopaminergic neurons: Neurophysiological identification and responses to drugs. In: Frontiers in catecholamine research (S. H. Snyder and E. Usdin, eds.), pp. 643–643. New York: Pergamon Press 1973Google Scholar
  2. Aghajanian, G. K., Bunney, B. S.: Pre- and postsynaptic feedback mechanisms in central dopaminergic neurons. In: Frontiers of neurology and neuroscience research (P. Seeman and G. M. Brown, eds.), pp. 4–11. Toronto: University Toronto Press 1974Google Scholar
  3. 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
  4. Björklund, A., Lindvall, O.: Dopamine in dendrites of substantia nigra neurons: Suggestions for a role in dendritic terminals. Brain Res. 83, 531–537 (1975)Google Scholar
  5. Bunney, B. S., Aghajanian, G. K.: d-Amphetamine-induced inhibition of central dopaminergic neurons: Mediation by a striato-nigral feedback pathway. Science 192, 391–393 (1976)Google Scholar
  6. Bunney, B. S., Aghajanian, G. K., Roth, R. H.: Comparison of effects of l-Dopa, amphetamine and apomorphine on firing rate of rat dopaminergic neurons. Nature New Biol. 245, 123–125 (1973a)Google Scholar
  7. Bunney, B. S., Walters, J. R., Roth, R. H., Aghajanian, G. K.: Dopaminergic neurons: Effect of antipsychotic drugs and amphetamine on single cell activity. J. Pharmacol. exp. Ther. 185, 560–571 (1973b)Google Scholar
  8. Carlsson, A.: Receptor-mediated control of dopamine metabolism. In: Pre- and postsynaptic receptors (E. Udsin and W. E. Bunney, Jr., eds.), pp. 49–66. New York: Marcel Dekker 1975Google Scholar
  9. Carlsson, A., Lindqvist, M.: Effect of chlorpromazine and haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta pharmacol. (Kbh.) 20, 140–144 (1963)Google Scholar
  10. 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
  11. Cedarbaum, J. M., Aghajanian, G. K.: Noradrenargic neurons of the locus coeruleus: Inhibition by epinephrine and activation by the α-antagonist piperoxane. Brain Res. 112, 413–419 (1976)Google Scholar
  12. Cheramy, A., Besson, M. J., Glowinski, J.: Increased release of dopamine from striatal dopaminergic terminals in the rat after treatment with a neuroleptic thioperazine. Europ. J. Pharmacol. 10, 206–214 (1970)Google Scholar
  13. Costa, E., Neff, N. H.: Isotopic and nonisotopic measurements of catecholamine biosynthesis. In: Biochemistry and pharmacology of the basal ganglia (E. Costa, L. Côté and M. D. Yahr, eds.), pp. 141–156. New York: Raven Press 1966Google Scholar
  14. Dahlström, A., Fuxe, K.: Evidence for the existence of monoamine neurons in the central nervous system. Acta physiol. scand. 64, suppl. 247, 1–85 (1965)Google Scholar
  15. Eccles, J. C.: The physiology of synapses. Berlin-Göttingen-Heidelberg: Springer 1964Google Scholar
  16. Farnebo, L. O., Hamberger, B.: Drug-induced changes in the release of 3H-monoamines from field stimulated rat brain slices. Acta physiol. scand. 371, 35–44 (1971)Google Scholar
  17. Faull, R. L. M., Laverty, R.: Changes in dopamine levels in the corpus striatum following lesions in the substantia nigra. Exp. Neurol. 23, 332–340 (1969)Google Scholar
  18. Geffen, L. B., Jessell, T. M., Cuello, A. C., Iversen, L. L.: Release of dopamine from dendrites in rat substantia nigra. Nature (Lond.) 260, 258–260 (1976)Google Scholar
  19. Groves, P. M., Wilson, C. J., Young, S. J., Rebec, G. V.: Self-inhibition by dopaminergic neurons. Science 190, 522–529 (1975)Google Scholar
  20. Haigler, H. J., Aghajanian, G. K.: Lysergic acid diethylamide and serotonin: A comparison of effects on serotonergic neurons and neurons receiving a serotonergic input. J. Pharmacol. exp. Ther. 188, 688–699 (1974)Google Scholar
  21. Iversen, L. L., Rogawski, M. A., Miller, R. J.: Comparison of the effects of neuroleptic drugs on pre- and postsynaptic dopaminergic mechanisms in the rat striatum. Molec. Pharmacol. 12, 251–262 (1976)Google Scholar
  22. 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, 454–563 (1972)Google Scholar
  23. Kebabian, J. W., Saavedra, J. M.: Dopamine-sensitive adenylate cyclase occurs in a region of substantia nigra containing dopaminergic dendrites. Science 193, 683–685 (1976)Google Scholar
  24. Kehr, W., Carlsson, A., Lindqvist, M., Magnusson, T., Atack, C. V.: Evidence for a receptor-mediated feedback control of striatal tyrosine hydroxylase activity. J. Pharm. Pharmacol. 24, 744–747 (1972)Google Scholar
  25. Korf, J., Zieleman, M., Westernik, B. H. C.: Dopamine release in the substantia nigra? Nature (Lond.) 260, 257–258 (1976)Google Scholar
  26. Murrin, L. C., Roth, R. H.: Dopaminergic neurons: Effects of electrical stimulation on dopamine biosynthesis. Molec. Pharmacol. 12, 463–475 (1976)Google Scholar
  27. Nybäck, H.: Effect of brain lesions and chlorpromazine on accumulation and disappearance of catecholamines formed in vivo from 14C-tyrosine. Acta physiol. scand. 84, 54–64 (1972)Google Scholar
  28. Roth, R. H., Walters, J. R., Aghajanian, G. K.: Effect of impulse flow in the release and synthesis of DA in the rat striatum. In: Frontiers of catecholamine research (S. H. Snyder and E. Usdin, eds.), pp. 567–574. New York-Oxford: Pergamon Press 1973Google Scholar
  29. Roth, R. H., Morgenroth III, V. H., Murrin, C. L.: The effects of antipsychotic drugs and impulse flow on the kinetics of striatal tyrosine hydroxylase. In: Antipsychotic drugs, pharmacodynamics and pharmacokinetics (G. Sedvall, ed.), pp. 133–145. Oxford-New York: Pergamon Press 1975Google Scholar
  30. Salmoiraghi, G. C., Weight, F.: Micromethods in neuropharmacology: An approach to the study of anesthesia. Anesthesiology 28, 54–64 (1967)Google Scholar
  31. Svensson, T. H., Bunney, B. S., Aghajanian, G. K.: Inhibition of both noradrenergic and serotonergic neurons in brain by the α-adrenergic agonist clonidine. Brain Res. 92, 291–306 (1975)Google Scholar
  32. Tasaki, K., Tsukahara, U., Ito, S., Wayner, M. J., Yu, W. Y.: A simple, direct and rapid method for filling microelectrodes. Physiol. Behav. 3, 1009–1010 (1968)Google Scholar
  33. Thomas, R. C., Wilson, V. J.: Precise localization of Renshaw cells with a new marking technique. Nature (Lond.) 206, 211–213 (1965)Google Scholar
  34. Von Voigtlander, P. F., Moore, K. E.: Involvement of nigrostriatal neurons in the vivo release of dopamine by amphetamine, amantadine and tyramine. J. Pharmacol. exp. Ther. 184, 542–552 (1973)Google Scholar
  35. Walters, J. R., Roth, R. H.: Dopaminergic neurons—alterations in the sensitivity of tyrosine hydroxylase to inhibition by endogenous dopamine after cessation of impulse flow. Biochem. Pharmacol. 25, 649–654 (1976)Google Scholar
  36. Walters, J. R., Roth, R. H., Aghajanian, G. K.: Dopaminergic neurons: Similar biochemical and histochemical effects of gammahydroxybutyrate and acute lesions of the nigro-neostriatal pathway. J. Pharmacol. exp. Ther. 186, 630–639 (1973)Google Scholar

Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • G. K. Aghajanian
    • 1
  • B. S. Bunney
    • 1
  1. 1.Yale University School of Medicine and Connecticut Mental Health CenterNew HavenUSA

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