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”.
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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 1973
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 1974
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)
Björklund, A., Lindvall, O.: Dopamine in dendrites of substantia nigra neurons: Suggestions for a role in dendritic terminals. Brain Res. 83, 531–537 (1975)
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)
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)
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)
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 1975
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)
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)
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)
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)
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 1966
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)
Eccles, J. C.: The physiology of synapses. Berlin-Göttingen-Heidelberg: Springer 1964
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)
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)
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)
Groves, P. M., Wilson, C. J., Young, S. J., Rebec, G. V.: Self-inhibition by dopaminergic neurons. Science 190, 522–529 (1975)
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)
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)
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)
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)
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)
Korf, J., Zieleman, M., Westernik, B. H. C.: Dopamine release in the substantia nigra? Nature (Lond.) 260, 257–258 (1976)
Murrin, L. C., Roth, R. H.: Dopaminergic neurons: Effects of electrical stimulation on dopamine biosynthesis. Molec. Pharmacol. 12, 463–475 (1976)
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)
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 1973
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 1975
Salmoiraghi, G. C., Weight, F.: Micromethods in neuropharmacology: An approach to the study of anesthesia. Anesthesiology 28, 54–64 (1967)
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)
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)
Thomas, R. C., Wilson, V. J.: Precise localization of Renshaw cells with a new marking technique. Nature (Lond.) 206, 211–213 (1965)
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)
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)
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)
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Aghajanian, G.K., Bunney, B.S. Dopamine “Autoreceptors”: Pharmacological characterization by microiontophoretic single cell recording studies. Naunyn-Schmiedeberg's Arch. Pharmacol. 297, 1–7 (1977). https://doi.org/10.1007/BF00508803
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DOI: https://doi.org/10.1007/BF00508803