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Distribution of D1-Like and D2 Receptors in the Monkey Brain: Implications for Cognitive Function in Schizophrenia

  • Ladislav Mrzljak
  • William E. Fieles
  • Amy M. Medd
  • Brian L. Largent
  • Zafar U. Khan

Dopamine D1-like (D1 and D5) and D2 (D2S and D2L) receptors are widely distributed in neuronal circuits of the primate dorsolateral prefrontal cortex (dlPFC) which is critically implicated in cognitive function such as working memory. Working memory is dependent on normal dopaminergic function in the dlPFC and consistently impaired in schizophrenia. Therefore, D1 and D2 receptors are considered to be good drug targets for improvement of cognitive function and treatment of psychosis in schizophrenia. Current data show that D1 and selective drug targeting both of these receptors may be optimal for improvement of cognitive function in schizophrenia. The differential distribution and function of short (D2S) and long (D2L) isoforms of the D2 receptor represent an opportunity to develop novel antipsychotics with improved efficacy and side effects. D5 receptors have complementary localization and function in the brain and therefore a nonbehaviors

Keywords

Dendritic Spine Glutamatergic Synapse Monkey Brain Dendritic Shaft Work Memory Function 
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.

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References

  1. Abi-Dargham, A., Mawlawi, O., Lomberdo, I., Gil, R., Martinez, D., Huang, Y., Hwang, D.R., Keilp, J., Kochan, L., Van Heertum, R., Gorman, J.M. and Laruelle, M. (2002) Prefrontal dopamine D1 receptors and working memory in schizophrenia. J. Neurosci. 22, 3708-3719.PubMedGoogle Scholar
  2. Agnati, L.F., Fuxe, K., Nicholson, C. and Sykova, E. (2000) Volume Transmission Revisited. Progress in Brain Research. Vol. 125, Elsevier, Amsterdam.Google Scholar
  3. Bergson, C., Mrzljak, L., Smiley, J.F., Pappy, M., Levenson, R. and Goldman-Rakic, P.S. (1995) Regional, cellular and subcellular variations in the distribution of D1 and D5 dopamine receptors in primate brain. J. Neurosci. 15, 7821-7836.PubMedGoogle Scholar
  4. Bordelon, J.R., Khan, Z.U. and Muly, E.C. (2006) D5 receptors are found with D1 in pyrami-dal cell spines of primate prefrontal cortex. Soc. Neurosci. Poster 332.18.Google Scholar
  5. Bunzow, J.R., Van Tol, H.H.M., Grandy, D.K., Albert, P., Salon, J., Christie, M., Machida, C.A., Neve, K.A. and Civelli, O. (1988) Cloning and expression of a rat D2 dopamine receptor. Nature 336, 783-787.CrossRefPubMedGoogle Scholar
  6. Castner, S.A. and Goldman-Rakic, P.S. (2004) Enhancement of working memory in aged monkeys by a sensitizing regimen of dopamine D1 receptor stimulation. J. Neurosci. 24, 1446-1450.CrossRefPubMedGoogle Scholar
  7. Castner, S.A., Williams, G.V. and Goldman-Rakic, P.S. (2000) Reversal of antipsychotic induced working memory deficits by short-term dopamine D1 receptor stimulation. Science 287, 2020-2022.CrossRefPubMedGoogle Scholar
  8. Castner, S.A., Goldman-Rakic, P.S. and Williams, G.V. (2004) Animal models of working memory: insights for targeting cognitive dysfunction in schizophrenia. Psychopharmacol-ogy 174, 111-125.Google Scholar
  9. Centonze, D., Grande, C., Saulle, E., Martin, A.B., Gubellini, P., Pavon, N., Pisani, A., Bernardi, G., Moratalla, R. and Calabresi, P. (2003) Distinct roles of D1 and D5 dopamine receptors in motor activity and striatal synaptic plasticity. J. Neurosci. 23, 8506-8512.PubMedGoogle Scholar
  10. Centonze, D., Usiello, A., Costa, C., Picconi, B., Erbs, E., Bernardi, G., Borrelli, E. and Calabresi, P. (2004) Chronic haloperidol promotes corticostriatal long-term potentiation by targeting dopamine D2L receptors. J. Neurosci. 24, 8214-8222.CrossRefPubMedGoogle Scholar
  11. Chen, G., Greengard, P. and Yan, Z. (2004) Potentiation of NMDA receptor currents by dopamine D1 receptors in prefrontal cortex. Proc. Natl. Acad. Sci. U.S.A. 101, 2596-2600.CrossRefPubMedGoogle Scholar
  12. Ciliax, B.J., Nash, N., Heilman, C., Sunahara, R., Harney, A., Tiberi, M., Rye, D.B., Caron, M.G., Niznik, H.B. and Levey, A.L. (2000) Dopamine D5 receptor immunolocalization in rat and monkey brain. Synapse 37, 125-145.CrossRefPubMedGoogle Scholar
  13. Gao, W., Krimer, L.S. and Goldman-Rakic, P.S. (2001) Presynaptic regulation of recurrent excitation by D1 receptors in prefrontal circuits. Proc. Natl. Acad. Sci. U.S.A. 98, 295-300.CrossRefPubMedGoogle Scholar
  14. Gazi, L. and Strange, P.G. (2002) Dopamine receptors. In: M.N. Pangolos and C.H. Davies (Eds.), Understanding G Protein-coupled Receptors and Their Role in the CNS. Oxford University Press, Oxford, pp. 264-285.Google Scholar
  15. Gingrich, J.A. and Caron, M.G. (1993) Recent advances in the molecular biology of dopamine receptors. Ann. Rev. Neurosci. 16, 299-321.CrossRefPubMedGoogle Scholar
  16. Giros, B., Sokoloff, P., Martres, M.-P., Riou, J.-F., Emorine, L.J. and Schwartz, J.-C. (1989) Alternative splicing directs the expression of two D2 receptor isoforms. Nature 342, 923-926.CrossRefPubMedGoogle Scholar
  17. Goldman-Rakic, P.S., Castner, S.A, Svensson, T.H., Siever, L.J. and Williams, G.V. (2004) Targeting the dopamine D1 receptor in schizophrenia: insights for cognitive dysfunction. Psychopharmacology 174, 3-16.CrossRefPubMedGoogle Scholar
  18. Khan, Z.U., Gutierrez, A., Martin, R., Penafiel, A., Rivera, A. and De La Calle, A. (1998a) Differential regional and cellular distribution of dopamine D2-like receptors. An immuno-cytochemical study of subtype specific antibodies in rat and human brain. J. Comp. Neurol. 402, 353-371.CrossRefPubMedGoogle Scholar
  19. Khan, Z.U., Mrzljak, L., Gutierrez, A., De La Calle, A. and Goldman-Rakic, P.S. (1998b) Prominence of the dopamine D2 short isoform in dopaminergic pathways. Proc. Natl. Acad. Sci. U.S.A. 95, 7731-7736.CrossRefPubMedGoogle Scholar
  20. Khan, Z.U., Gutierrez, A., Martin, R., Penafiel, A., Rivera, A. and De La Calle, A. (2000) Dopamine D5 receptors of rat and human brain. Neuroscience 100, 689-699.CrossRefPubMedGoogle Scholar
  21. Laplante, F., Sibley, D.R. and Quirion, R. (2004) Reduction in acetylcholine release in the hippocampus of dopamine D5 receptor-deficient mice. Neuropsychopharmacology 29, 1620-1627.CrossRefPubMedGoogle Scholar
  22. Lee, F.J.S, Xue, S., Pei, L., Vukusic, B., Chery, N., Wang, Y., Wang, Y.T., Niznik, H.B., Yu, A. and Liu, F. (2002) Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor. Cell 111, 219-230.CrossRefPubMedGoogle Scholar
  23. Levey, A.I., Hersch, S.M., Rye, D.B., Sunahara, R.K., Niznik, H.B., Kitt, C.A., Price, D.L., Maggio, R., Brann, M.R. and Ciliax, B.J. (1993) Localization of D1 and D2 dopamine re-ceptors in brain with subtype-specific antibodies. Proc. Natl. Acad. Sci. U.S.A. 90, 8861-8865.CrossRefPubMedGoogle Scholar
  24. Monsma, F.J., McVittie, L.D., Gerfen, C.R., Mahan, L.C. and Sibley, D.R. (1989) Multiple dopamine D2 receptors produced by alternative RNA splicing. Nature 342, 926-929.CrossRefPubMedGoogle Scholar
  25. Mrzljak, L., Bergson, C., Pappy, M., Huff, R., Levenson, R. and Goldman-Rakic, P.S. (1996) Localization of dopamine D4 receptors in GABAergic neurons of the primate brain. Nature 381, 245-248.CrossRefPubMedGoogle Scholar
  26. Mrzljak, L., Fieles, W.E., Khan, Z.U. and Medd, A.M. (2006) Association of D5 dopamine receptors with pre- and postsynaptic elements of glutamatergic synapses. Soc. Neurosci. Poster. 332.22.Google Scholar
  27. Muly III C.E., Szigeti, K. and Goldman-Rakic, P.S. (1998) D1 receptor in interneurons of macaque prefrontal cortex: distribution and subcellular localization. J. Neurosci. 18, 10553-10565.PubMedGoogle Scholar
  28. Nusser, Z., Sieghart, W., Stephenson, F.A. and Somogyi, P. (1996) The α-6 subunit of the GABAa receptor is concentrated in both inhibitory and excitatory synapses on cerebellar granule cells. J. Neurosci. 16, 103-114.PubMedGoogle Scholar
  29. Paspalas, C.D. and Goldman-Rakic, P.S. (2004) Microdomains for dopamine volume neuro-transmission in primate prefrontal cortex. J. Neurosci. 24, 5292-5300.CrossRefPubMedGoogle Scholar
  30. Paspalas, C.D. and Goldman-Rakic, P.S. (2005) Presynaptic D1 dopamine receptor in primate prefrontal cortex: target-specific expression in the glutamatergic synapse. J. Neurosci. 25, 1260-1267.CrossRefPubMedGoogle Scholar
  31. Pei, L., Lee, F.J.S., Moszczynska, A., Vukusic, B. and Liu, F. (2004) Regulation of dopamine D1 receptor function by physical interaction with the NMDA receptors. J. Neurosci. 24, 1149-1158.CrossRefPubMedGoogle Scholar
  32. Petralia, R.S., Rubio, M.E., Wang, Y.-X. and Wenthold, R.J. (2000) Regional and synaptic expression of ionotropic glutamate receptors. In: O.P. Ottersen and J. Storm-Mathisen (Eds.), Handbook of Chemical Neuroanatomy: Glutamate. Vol. 18, Elsevier, Amsterdam, pp. 145-182.Google Scholar
  33. Scott, L., Sol Kruse, M., Forssberg, H., Brismar, H., Greengard, P. and Aperia, A. (2002) Selective up-regulation of dopamine D1 receptors in dendritic spines by NMDA receptor activation. Proc. Natl. Acad. Sci. U.S.A. 99, 1661-1664.CrossRefPubMedGoogle Scholar
  34. Sesack, S.R., Aoki, C. and Pickel, V.M. (1994) Ultrastructural localization of D2 receptor-like immunoreactivity in midbrain dopamine neurons and their striatal targets. J. Neurosci. 14, 88-106.PubMedGoogle Scholar
  35. Sesack, S.R., Snyder, C.L. and Lewis, D.A. (1995) Axon terminals immunolabeled for dopa-mine or tyrosine hydroxylase synapse of GABA-immunoreactive dendrites in rat and monkey. J. Comp. Neurol. 363, 264-280.CrossRefPubMedGoogle Scholar
  36. Smiley, J.F., Levey, A.I., Ciliax, B.J. and Goldman-Rakic, P.S. (1994) D1 dopamine receptor immunoreactivity in human and monkey cerebral cortex: predominant and extrasynaptic localization in dendritic spines. Proc. Natl. Acad. Sci. U.S.A. 91, 5720-5724.CrossRefPubMedGoogle Scholar
  37. Usiello, A., Balk, J., Rouge-Pont, F., Picetti, R., Dierich, A., LeMeur, M., Piazza, P.V. and Borrelli, E. (2000) Distinct function of the two isoforms of dopamine D2 receptors. Nature 408, 199-203.CrossRefPubMedGoogle Scholar
  38. Wang, M., Vijayraghavan, S. and Goldman-Rakic, P.S. (2004) Selective D2 receptor actions on the functional circuitry of working memory. Science 303, 853-856.CrossRefPubMedGoogle Scholar
  39. Xu, R., Hranilovic, D., Fetsko, L.A., Bucan, M. and Wang, Y. (2002) Dopamine D2S and D2L receptors may differentially contribute to the actions of antipsychotic and psychotic agents in mice. Mol. Psychiatry 7, 1075-1082.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Ladislav Mrzljak
    • 1
  • William E. Fieles
    • 1
  • Amy M. Medd
    • 1
  • Brian L. Largent
    • 1
  • Zafar U. Khan
    • 2
  1. 1.Department of Neuroscience BiologyAstraZeneca Pharmaceuticals R&DWilmingtonUSA
  2. 2.Department of MedicineSchool of MedicineSpain

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