Inhibitory Role of Dopaminergic D2 Receptors in the Expression of Glutamic Acid Decarboxylase and Preproenkephalin mRNA in the Rat Striatum

  • Jocelyne Caboche
  • Philippe Vernier
  • Jean-François Julien
  • Monique Rogard
  • Jacques Mallet
  • Marie-Jo Besson
Part of the Advances in Behavioral Biology book series (ABBI, volume 39)


Dopamine (DA) contained in the dense network of DA fibers innervating the striatum has been shown to play a major role in the regulation of striatal neuron activity. This has been approached by analyzing either changes in electrophysiological properties of neurons (Bernardi et al., 1978; Calabresi et al., 1988) or changes in biochemical parameters such as the levels and/or the synthesis (Hong et al., 1978a and b; Hanson et al., 1988; Li et al., 1987) or the release (Lehman and Langer, 1983; Girault et al., 1986a) of specific neurotransmitters localized in striatal neurons. A useful tool in understanding the regulation of neuronal activity is now offered by molecular biology which allows the identification of specific mRNAs, reflecting earlier events than neurotransmitter contents. In this study, we tried to elucidate the DA receptor subtype which mediates dopaminergic modulation of the expression of messengers encoding glutamic acid decarboxylase (GAD) and preproenkephalin (PPE), two major markers contained in projection neurons of the striatum (Fonnum et al., 1974; Cuello et al. 1978). This analysis has been initiated by previous findings showing that a 6-hydroxydopamine (6-OHDA) lesion of nigrostriatal DA neurons produced increased levels of mRNAs encoding GAD (Vernier et al., 1988) and PPE (Angulo et al. 1986; Young et al., 1986; Normand et al. 1988), and that these effects could be reproduced by chronic treatments with haloperidol (Sabol et al., 1983; Tang et al., 1983; Sivam et al., 1986; Normand et al., 1987; Morris et al., 1988; Vernier unpublished observations). These previous studies suggested an inhibitory control of DA on the expression of both GAD- and PPE-mRNA. The action of DA being mediated by an interaction with at least two receptor subtypes, coupled to different second messenger systems (Stoof and Kebabian, 1981), it was of interest to elucidate the receptor subtype involved in these effects.


Ventral Striatum Glutamic Acid Decarboxylase Dorsal Striatum Striatal Neuron Striatopallidal Neuron 
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  1. Angulo, J.A., Davis, L.G., Burkhart, B.A., Christoph, G.R., 1986, Reduction of striatal dopaminergic neurotransmission elevates striatal proenkephalin mRNA, Eur. J. Pharmacol., 130: 343 – 344.CrossRefGoogle Scholar
  2. Aronin, N., DiFiglia, M., Graveland, G.A., Schwartz, W.J. and Wu, J.-Y., 1984, Localization of immunoreactive enkephalins in GABA synthesizing neurons of the rat neostriatum, Brain Res., 300: 376 – 380.PubMedCrossRefGoogle Scholar
  3. Beckstead, R.M., Wooten, G.F., and Trugman, J.M., 1988, Distribution of Dl and D2 dopamine receptors in the basal ganglia of the cat determined by quantitative autoradiography, I. Comp. Neurol., 268: 131 – 145.CrossRefGoogle Scholar
  4. Bernardi, G., Marciani, M.G., Morocutti, C., Pavone F., and Stanzione, P., 1978, The action of dopamine on rat caudate neurons intracellularly recorded, Neurosci. Letts, 8: 235 – 240.CrossRefGoogle Scholar
  5. Björklund, A., and Lindvall, O., Dopamine-containing systems in the CNS., 1984, "Handbook of Chemical Neuroanatomy, Vol. 2, Classical Neurotransmitters in the CNS", Björklund A. and Hökfelt T. eds, Part I, pp. 55–112. Elsevier, Amsterdam.Google Scholar
  6. Boyson, S.J., Mc Gonigle, P., and Molinoff, P.B., 1986, Quantitative autoradiographic localization of the D1 and D2 subtypes of dopamine receptors in rat brain, L Neurosci., 6: 3177 – 3188.Google Scholar
  7. Calabresi, P, Mercuri, N., Stanzione, P., Stefeni, A., and Bernardi, G., 1986, Intracellular studies on the dopamine-induced firing inhibition of neostriatal neurons in vitro: evidence for Dl receptor involvement, Neurosci., 20: 757 – 771.CrossRefGoogle Scholar
  8. Calabresi, P., Benedetti, M., Mercuri, N.B., and Bernardi, G., 1988, Endogenous dopamine and dopaminergic agonists modulate synaptic excitation in neostriatum: intracellular studies from naive and catecholamine-depleted rats, Neurosci., 27: 145 – 157.CrossRefGoogle Scholar
  9. Chesselet, M.F. and Robbins, E., 1989, Characterization of striatal neurons expressing high levels of glutamic acid decarboxylase messenger RNA, Brain Res., 492: 237 – 244.PubMedCrossRefGoogle Scholar
  10. Christensen, A.V., Amt, J., Hyttel, J., Larsen, J.-J., and Svendsen, O., 1984, Pharmacological effects of a specific dopamine D-1 antagonist SCH 23390 in comparison with neuroleptics, Life Sci., 34: 1529 – 1540.PubMedCrossRefGoogle Scholar
  11. Comb, M., Mermod, N., Hyman, S.E., Pearlberg, J., Ross, M.E., and Goodman, H.M., 1988, Proteins bound at adjacent DNA elements act synergistically to regulate human proenkephalin cAMP inducible transcription, EMBO J. 7: 3793 – 3805.PubMedGoogle Scholar
  12. Cuello, A.C., and Paxinos, G., 1978, Evidence for a long Leu-enkephalin striatopallidal pathway in rat brain, Nature, 271: 178 – 180.PubMedCrossRefGoogle Scholar
  13. Dal Toso, R., Sommer, B., Ewert, M., Herb, A., Pritchett, D.B., Bach, A., Shivers, B.D., and Seeburg, P., 1989, The dopamine D2 receptor: two molecular forms generated by alternative splicing, EMBO J., 8: 4025 – 4034.PubMedGoogle Scholar
  14. Dawson, T.M., Gehlert, D.R., McCabe, R.T., Barnett, A., and Wamsley, J.K., 1986, D-1 dopamine receptors in the rat brain: a quantitative autoradiographic analysis, J. Neurosci., 6: 2353 – 2365.Google Scholar
  15. Faucon Biguet, N., Buda, M., Lamouroux, A., Samolyk D., and Mallet, J., 1986, Time course of the changes of TH mRNA in rat brain and adrenal medulla after a single injection of reserpine, EMBO J., 5: 287 – 291.Google Scholar
  16. Freedman, J.E. and Weight, F.F., 1988, Single K+ channels activaed by D2 copmaine receptors in acutely dissociated neurons from rat corpus striatum, Proc. Natl. Acad. Sci. USA, 85: 3618 – 3622.PubMedCrossRefGoogle Scholar
  17. Fonnum, F., Gottesfeld, Z., and Grofova, I., 1974, Distribution of glutamate decarboxylase, choline acetyltransferase and aromatic amino-acid decarboxylase in the basal ganglia of normal and operated rats: evidence for striatopallidal, striatoentopeduncular and striatonigral GABAergic fibers, Brain Res. 143: 125 – 138.CrossRefGoogle Scholar
  18. Gale, K., Guidotti, A., and Costa, E., 1977, Dopamine-sensitive adenylate cyclase: location in substantia nigra, Science, 195: 503 – 507.PubMedCrossRefGoogle Scholar
  19. Girault, J.A., Spampinato, U., Savaki, H.E., Glowinski, J., and Besson, M.J., 1986a, In vivo release of (3H)o-aminobutyric acid in the rat neostriatum - I.Characterization and topographical heterogeneity of the effects of dopaminergic and cholinergic agents, Neuroscience, 19: 1101–1108.PubMedCrossRefGoogle Scholar
  20. Girault, J.A., Barbeito, L., Spampinato, U., Gozlan, H., Glowinski, J., and Besson, M.-J., 1986b, In vivo release of endogenous amino acids from the rat striatum: further evidence for a role of glutamate and aspartate in corticostriatal neurotransmission, J. Neurochem., 47: 98 – 106.CrossRefGoogle Scholar
  21. Hanson, G.R., Merchant, K.M., Letter, A.A., Bush, L., and Gibb, J.W., 1988, Characterization of methamphetamine effects on the striatal-nigral dynorphin system, Eur. J. Pharmacol., 155: 11 – 18.PubMedCrossRefGoogle Scholar
  22. Hong, J.S., Yang, H.-Y. T., Fratta, W., and Costa E., 1978a, Rat striatal methionineenkephalin content after chronic treatment with cataleptogenic and noncataleptogenic antischizophrenic drugs, J. Pharmacol. exp. Ther., 205: 141 – 147.Google Scholar
  23. Hong, J.S., Yang, H.Y.T., and Costa, E., 1978b, Substance P content of substantia nigra after chronic treatment with antischizophrenic drugs, Neuropharmacol., 17: 83 – 85.CrossRefGoogle Scholar
  24. Imperato, A., Mulas, A., and Di Chiara, G., 1987, The D-1 antagonist SCH 23390 stimulates while the D-1 agonist SKF 23393 fails to affect dopamine release in the dorsal caudate of freely moving rats, Eur. J. Pharmacol., 142: 177 – 181.PubMedCrossRefGoogle Scholar
  25. Lehmann, J., and Langer, S.Z., 1983, The striatal cholinergic interneurons: synaptic target of dopaminergic terminals?, Neuroscience, 10: 1105 – 1120.PubMedCrossRefGoogle Scholar
  26. Li, S., Sivam, S.P., McGinty, J.F., Huang Y.S., and Hong, J.S., 1987, Dopaminergic regulation of tachykinin metabolism in the striatonigral pathway, k Pharmacol. Exp. Ther., 243: 792 – 798.Google Scholar
  27. Morris, B.J., Höllt, V., and Herz, A., 1988, Dopaminergic regulation of striatal proenkephalin mRNA and prodynorphin mRNA: contrasting effects of D1 and D2 antagonists, Neurosci., 25: 525 – 532.CrossRefGoogle Scholar
  28. Normand, E., Popovici, T., Fellmann, D., and Bloch, B., 1987, Anatomical study of enkephalin gene expression in the rat forebrain following haloperidol treatment, Neurosci. Lett., 83: 232 – 236.PubMedCrossRefGoogle Scholar
  29. Normand, E., Popovici, T., Onteniente, B., Fellmann, D., Piatier-Tonneau, D., Auffray, C., and Bloch, B., 1988, Dopaminergic neurons of the substantia nigra modulate preproenkephalin A gene expression in rat striatal neurons, Brain Res., 439: 39–46.PubMedCrossRefGoogle Scholar
  30. Pizzi, M., Da Prada, M., Valerio, A., Memo, M., Spano, P.F., and Haefely, W.E.,1988, Dopamine D2 receptor stimulation inhibits inositol phosphate generating system in rat striatal slices, Br. Res., 456: 235–240.CrossRefGoogle Scholar
  31. Rowlands, G.J., and Roberts, P.J., 1980, Activation of dopamine receptors inhibits calcium-dependant glutamate release from cortico-striatal terminals in vitro, Eur. J. Pharmacol. 62: 241 – 242.PubMedCrossRefGoogle Scholar
  32. Sabol, S.L., Yoshikawa, K., and Hong, J.-S., 1983, Regulation of methionineenkephalin precursof messenger RNA in rat striatum by haloperidol and lithium, Biochem. and Byophys. Res. Communic., 113: 391 – 399.CrossRefGoogle Scholar
  33. Savasta, M., Dubois, A., and Scatton, B., 1986, Autoradiographic localization of D1 dopamine receptors in the rat brain with (3H)SCH 23390, Brain Res., 375: 291–301.PubMedCrossRefGoogle Scholar
  34. Seeman, P., 1980, Brain dopamine receptors, Pharmacol. Rev., 32: 229 – 313.PubMedGoogle Scholar
  35. Sivam, S.P., Strunk, C., Smith, D.R., and Hong, J.S., 1986, Proenkephalin-A gene regulation in the rat striatum: influence of lithium and haloperidol, Molec. Pharmacol., 30: 186–191.Google Scholar
  36. Stoof, J.C., and Kebabian J.W., 1981, Opposing roles for D1 and D2 dopamine receptors in efflux of cyclic AMP from rat neostriatum, Nature, 294: 366 – 368.PubMedCrossRefGoogle Scholar
  37. Tang, F., Costa, E., and Schwartz, J.P., 1983, Increase of proenkephalin mRNA and enkephalin content of rat striatum after daily injection of haloperidol for 2 to 3 weeks, Proc. Natl. Acad. Sci. USA, 80: 3841 – 3844.PubMedCrossRefGoogle Scholar
  38. Uhl, G.R., Navia, B., and Douglas, J., 1988, Differential expression of preproenkephalin and preprodynorphin mRNAs in striatal neurons: high levels of preproenkephalin expression depend on cerebral cortical afferents, L Neurosci., 8: 4755 – 4564.Google Scholar
  39. Vernier, P., Julien, J.F., Rataboul, P., Fourrier, O., Feuerstein, C., and Mallet, J., 1988, Similar time course changes in striatal levels of glutamic acid decarboxylase and proenkephalin mRNA following dopaminergic deafferentation in the rat, I. Neurochem., 51: 1375 – 1380.CrossRefGoogle Scholar
  40. Young, W.S., Bonner, T.I., and Brann, M.R., 1986, Mesencephalic dopamine neurons regulate the expression of neuropeptide mRNAs in the rat forebrain, Proc. Natl. Acad. Sci. USA, 83: 9827 – 9831.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Jocelyne Caboche
    • 1
  • Philippe Vernier
    • 2
  • Jean-François Julien
    • 2
  • Monique Rogard
    • 1
  • Jacques Mallet
    • 2
  • Marie-Jo Besson
    • 1
  1. 1.Laboratoire de Neurochimie-AnatomieInstitut des Neurosciences Université P. et M. CurieParisFrance
  2. 2.Departement de Génétique MoléculaireLaboratoire de Neurobiologie Cellulaire et Moléculaire C.N.R.S.Gif-sur-YvetteFrance

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