Abstract
The microdialysis technique was utilized to study the local effects of D1 and D2 family type dopamine (DA) receptor (R) ligands on the in vivo release of endogenous glutamate (GLU) and aspartate (ASP) from rat substantia nigra (SN). Addition to the dialysis perfusion solution of either D1-R and D2-R agonists, such as SKF-38393 (50 and 100 μM) and Quinpirole (5 and 10 μM), resulted in dose-dependent increases in extracellular concentrations of GLU and ASP, respectively. The SKF-38393 and Quinpirole-induced effects were reduced by SCH-23390 (0.5 μM), a D1-R antagonist, and by Spiperone (1.0 μM), a D2-R antagonist, respectively. However, SCH-23390 and Spiperone did increase GLU and ASP extracellular concentrations. Local infusion with Tetrodotoxin (TTX) (1.0 μM), a blocker of voltage-dependent Na+ channels, increased basal extracellular levels of GLU. In addition, co-infusion of TTX and SKF-38393 evoked increases in extracellular GLU levels higher than those observed after SKF-38393 alone. Finally, chemical lesions of nigral DA cells with 6-OH-DA increased the basal extracellular levels of GLU. It is proposed that the release of GLU and ASP from SN may be regulated by D1- and D2-receptors present in this basal ganglia structure. In addition, part of the D1 receptors present in SN might be located presynaptically on GLU-containing nerve endings.
Similar content being viewed by others
References
Alexander, G. E., and Crutcher, M. D. 1990. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends. Neurosci. 13:266–271.
Albin, R. L., Young, A. B., and Penny, J. B. 1989. The functional anatomy of basal ganglia disorders. Trends. Neurosc. 12:366–375.
Gale, K. 1988. Progression and generalization of seizure discharge: anatomical and neurochemical substrates. Epilepsia 29: Suppl. 2, 515–534.
Abarca, J., and Bustos, G. 1985. Release ofd-[3H]aspartic acid from the rat substantia nigra: effect of veratridine-evoked depolarization and cortical ablation. Neurochem. Int. 7:299–306.
Carter, C. J. 1980. Glutamatergic pathways from the medial prefrontal cortex to the anterior striatum, nucleus accumbens and substantia nigra. Br. J. Pharmacol. 70:50P.
Fiedler, J., and Bustos, G. 1991. Cortical ablation reduces veratridine evoked release of endogenous glutamate from superfused nigra slices. Neurosc. Lett. 22:96–98.
Fonnum, F., Soreide, A., Krale, I., Walker, J., and Walaas, I. 1981. Glutamate in cortical fibers. Adv. Biochem. Psychopharmacol 27: 29–42.
Kornhuber, J., Jin-Soo, K., Kornhuber, M. E., and Kornhuber, H. H. 1984. The corticonigral projection: reduced glutamate content in the substantia nigra following frontal cortex ablation in the rat. Brain Res. 322:124–126.
Bustos, G., Abarca, J., Fiedler, J., and Araneda, R. 1988. Neurochemistry of the substantia nigra: interrelations between excitatory amino acids, N-methyl-D-aspartate receptors and intrinsic neuronal systems. Arch. Biol. Med. Exp. 21:59–64.
Klockgether, T., and Turski, L. 1989. Excitatory amino acids and the basal ganglia: implications for the therapy of Parkinson's disease. Trends. Neurosci. 12:285–286.
Nakanishi, H., Kita, H., and Kitai, S. T. 1987. Intracellular study of substantia nigra pars reticulata neurons in an in vitro slice preparation: electrical membrane properties and response characteristics to subthalamic stimulation. Brain Res. 437:45–55.
Smith, Y., and Parent, A. 1988. Neurons of the subthalamic nucleus in primates display glutamate but not GABA immunoreactivity. Brain Res. 453:353–356.
Nieoullon, A., Cheramy, A., and Glowinski, J. 1978. Release of dopamine evoked by electrical stimulation of the motor and visual areas of the cerebral cortex in both caudate nuclei and in the substantia nigra of the rat. Brain. Res. 145:69–83.
Araneda, R., and Bustos, G. 1989. Modulation of dendritic release of dopamine by N-methyl-D-aspartate receptors in rat substantia nigra. J. Neurochem. 52:962–970.
Abarca, J., and Bustos, G. 1988. Modulation of excitatory amino acid release by endogenous dopamine and D1 receptors in substantia nigra. Arch. Biol. Med. Exp. 21:R-275.
Abarca, J., and Bustos, G. 1990. Depolarization evoked release of D-[3H] aspartate from slices of substantia nigra: effects of dopamine receptor ligands. Neurochem. Int. 16:253–261.
Cheramy, A., Leviel, U., and Glowinski, J. 1981. Dendritic release of dopamine in the substantia nigra. Nature 289:537–542.
Geffen, L. B., Jessell, T. M., Cuello, A. C., and Iversen, L. L. 1976. Release of dopamine from dendrites in rat substantia nigra. Nature 260:258–260.
Altar, C. A., and Hauser, K. 1987. Topography of substantia nigra innervation by D1 receptor-containing striatal neurons. Brain Res. 410:1–11.
Dubois, A., Savasta, M., Curet, O., and Scatton, B. 1986. Autoradiographic distribution of D2 dopamine receptors. Neuroscience 19:379–386.
Murrin, L. C., Gale, K., and Kuhar, M. J. 1979. Autoradiographic localization of neuroleptic and dopamine receptors in the caudateputamen and substantia nigra: effect of lesions. Eur. J. Pharmac. 60:229–235.
Quik, M., and Iversen, L. L. 1979. Regional study of3H-spiperone binding and the dopamine-sensitive adenylate cyclase in rat brain. Eur. J. Pharmacol. 56:323–330.
Abarca, J., and Bustos, G. 1991. Microdialysis as an experimental tool to studyin vivo chemical interactions between GLUergic and DAergic neurons in rat brain substantia nigra. Arch. Biol. Med. Exp. 24:R-122.
Abarca, J., and Bustos, G. 1992. Role of dopamine receptors and voltage-dependent Na+ channels on GLU and ASP release in rat substantia nigra. Abstr. XXXV Annu. Meeting Chilean Biolog. Soc., R-91.
Paxinos, G., and Watson, C. 1982. The Rat Brain in Stereotaxic Coordinates. Academic Press, Sydney.
Bradberry, Ch. W., and Roth, R. H. 1989. Cocaine increases extracellular dopamine in rat nucleus accumbens and ventral tegnental area as shown by in vivo microdialysis. Neurosc. Lett. 103: 97–102.
Bustos, G., Abarca, J., Forray, M. L., Gysling, K., Bradberry, Ch. V., and Roth, R. H. 1992. Regulation of excitatory amino acid release by N-methyl-D-aspartate receptors in rat striatum: in vivo microdialysis studies. Brain Res. 585:105–115.
Church, W. H., and Justice, J. B. 1987. Rapid sampling and determination of extracellular dopamine in vivo. Anal. Chem. 59: 712–716.
Lindroth, P., and Mopper, K. 1979. High performance liquid chromatographic determination of subpicomole amounts of amino acids by precolumn fluorescence derivatization with o-phthalaldehyde. Anal. Chem. 51:1667–1674.
Lista, A., Abarca, J., Ramos, C., and Daniels, A. J. 1986. Rat striatal dopamine and tetrahydrobiopterin content following an intrastriatal injection of manganese chloride. Life Sci. 38:2121–2127.
Sibley, D. R., Leff, S. E., and Creese, I. 1982. Interactions of novel dopaminergic ligands with D-1 and D-2 dopamine receptors, Life Sci. 31:637–645.
Ioro, L. C., Barnett, A., Leitz, F. H., Houser, U. P., and Korduba, C. A. 1983. SCH-23390, a potential benzazepine antipsychotic with unique interactions of dopaminergic systems. J. Pharmac. Exp. Ther. 226:462–468.
O'Boyle, K. M., and Waddington, I. L. 1987. [3H]SCH-23390 binding to human putamen D-1 dopamine receptors: Stereochemical and Structure-affinity relationships among 1-Phenyl-1H-3-Benzazepine derivatives as a guide to D-1 receptor topography. J. Neurochem. 48:1039–1042.
Porceddu, M. L., Giorgi, O., Ongini, E., Mele, S., and Biggio, G. 1986. [3H]SCH-23390 binding sites in the rat substantia nigra: evidence for a presynaptic localization and innervation by dopamine. Life Sci. 39:321–328.
Quik, M., Emson, P. C., and Joyce, E. 1979. Dissociation between the presynaptic dopamine-sensitive adenylate cyclase and [3H]spiperone binding sites in the rat substantia nigra. Brain Res. 167:355–365.
Nagahama, S., Chen, Y. F., Lindheimer, M. D., and Oparil, S. 1986. Mechanism of the pressor action of LY-171555, a specific dopamine D2 receptor agonist, in the conscious rat. J. Pharmacol. Exp. Ther. 236:735–743.
Ruffolo, R. H., and Sharr, C. J. 1983. Relative potency of LY-171555 at dopamine-DA2 and histamine-H2 receptors. Eur. J. Pharmacol. 92:295–301.
Grace, A. A., and Bunney, B. S. 1983. Intracellular and extracellular electrophysiology of nigral dopamine neurons. Identification and characterization. Neuroscience 10:301–315.
Hollerman, J. R., and Grace, A. A. 1990. The effects of dopaminedepleting brain lesions on the electrophysiological activity of rat substantia nigra dopamine neurons. Brain Res. 533:203–212.
Weick, B. G., Engber, T. M., Susel, Z., Chase, T. N., and Walters, J. R. 1990. Responses of substantia nigra pars reticulata neurons to GABA and SKF-38393 in 6-hydroxydopamine-lesioned rats are differentially affected by continuous and intermittent levodopa administration. Brain Res. 523:16–22.
Paulsen, R. E., and Fonnum, F. 1989. Role of glial cells for the basal and Ca2+-dependent K+-evoked release of transmitter amino acids investigated by microdialysis. J. Neurochem. 52:1823–1829.
Nicholls, D. G. 1989. Release of glutamate, aspartate and gamma-aminobutyric acid from isolated nerve terminals. J. Neurochem. 52:331–341.
Wilkinson, R. J., and Nicholls, D. G. 1989. Compartmentation of glutamate and aspartate within cerebral cortical synaptosomes: evidence for a non-cytoplasmic origin for the calcium releasable pool of glutamate. Neurochem. Int. 15:191–197.
Morari, M., O'Connor, W. T., Ungerstedt, U., and Fuxe, K. 1993. N-methyl-D-aspartic acid differentially regulates extracellular dopamine, GABA and Glutamate levels in the dorsolateral neostriatum of the halothane-anesthetized rat: an in vivo microdialysis study. J. Neurochem. 60:1884–1893.
Aghajanian, G. K., and Bunney, B. S. 1977. Dopamine autoreceptors: pharmacological characterization by microiontophoretic single cell recording studies. Naunyn-Schmiedeberg's Arch. Pharmacol. 297:1–7.
Martres, M. P., Boothenet, M. L., Soles, N., Sokoloff, P., and Schwartz, J. C. 1985. Widespread distribution of brain dopamine receptors evidenced with [125I] iodosulpiride, a highly selective ligand. Science 228:752–755.
Weiner, D. M., Levey, A. I., Sunahara, R. K., Niznik, H. B., O'Dowd, B. F., Seeman, P., and Brann, M. R. 1991. D1 and D2 dopamine receptor mRNA in rat brain. Proc. Natl. Acad. Sci., U.S.A., 88:1859–1863.
Filloux, F. M., Wamsley, J. K., and Dawson, T. M. 1987. Presynaptic and postsynaptic D1 dopamine receptors in the nigrostriatal system of the rat brain: a quantitative autoradiographic study using the selective D1 antagonist [3H]SCH-23390. Brain Res. 408:205–209.
Strange, P. G. 1991. D1/D2 dopamine receptor interaction at the biochemical level. Trends. Pharmacol. Sci 12:48–49.
Waddington, J. W. 1986. Behavioural correlates of the action of selective D-1 dopamine receptor antagonists. Biochem. Pharmacol. 35:3661–3667.
Jacobson, I., and Hamberger, A. 1985. Kainic acid-induced changes of extracellular amino acid levels, evoked potentials and EEG activity in the rabbit olfactory bulb. Brain Res. 348:289–296.
Lehmann, A., Isaccsson, H., and Hamberger, A. 1983. Effects of in vivo administration of kainic acid on the extracellular amino acid pool in the rabbit hippocampus. J. Neurochem. 40:1314–1320.
Yamamoto, B. K., Davy, S. 1992. Dopaminergic modulation of glutamate release in striatum as measured by microdialysis. J. Neurochem. 58:1736–1742.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Abarca, J., Gysling, K., Roth, R.H. et al. Changes in extracellular levels of glutamate and aspartate in rat substantia nigra induced by dopamine receptor ligands: In vivo microdialysis studies. Neurochem Res 20, 159–169 (1995). https://doi.org/10.1007/BF00970540
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00970540