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Involvement of Dopamine Transporters in Psychiatric Disorders

  • Chapter
Contemporary Issues in Modeling Psychopathology

Part of the book series: Neurobiological Foundation of Aberrant Behaviors ((NFAB,volume 1))

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Abstract

The plasma membrane dopamine transporter (DAT) and the vesicular monoamine transporter (VMAT2) are key regulators of dopamine neurotransmission. DAT acts to terminate the actions of dopamine by rapidly removing dopamine from the synapse, while VMAT2 mediates loading of dopamine from the cytoplasm to vesicles for storage and subsequent release. Recent data from our laboratories and others’ suggest that perturbation of the tightly regulated balance between these two transporters alters dopamine function and may predispose the neuron to damage by a variety of insults. While the selective degeneration of DAT- and VMAT2- expressing dopamine nerve terminals in the striatum that leads to Parkinson’s disease is the most well known example, several other disorders may result or be exacerbated by the altered transporter function. Data from cell culture, knockout models, and human studies reveal that DAT and VMAT2 expression can predict the selective vulnerability of neuronal populations. Here, we review the role of DAT and VMAT2 in neurodegenerative disease and suggest how these findings can be applied to our understanding of psychiatric disorders.

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References

  • Backman, L., Robins-Wahlin, T. B., Lundin, A., Ginovart, N., Farde, L. (1997). Cognitive deficits in Huntington’s disease are predicted by dopaminergic PET markers and brain volumes. Brain 120, 2207–17.

    Article  PubMed  Google Scholar 

  • Barrickman, L., Noyes, R., Kuperman, S., Schumacher, E., Verda, M. (1991). Treatment of ADHD with fluoxetine: a preliminary trial. J Am Acad Child Adolesc Psychiatry 30, 762–7.

    PubMed  CAS  Google Scholar 

  • Ben-Shachar, D., Zuk, R., Glinka, Y. (1995). Dopamine neurotoxicity: inhibition of mitochondrial respiration. J Neurochem 64, 718–23.

    Article  PubMed  CAS  Google Scholar 

  • Blakely, R. D., Berson, H. E., Fremeau, R. T., Jr., Caron, M. G., Peek, M. M., Prince, H. K., Bradley, C. C. (1991). Cloning and expression of a functional serotonin transporter from rat brain. Nature 354, 66–70.

    Article  PubMed  CAS  Google Scholar 

  • Blum, K., Braverman, E. R., Wu, S., Cull, J. G., Chen, T. J., Gill, J., Wood, R., Eisenberg, A., Sherman, M., Davis, K. R., Matthews, D., Fischer, L., Schnautz, N., Walsh, W., Pontius, A. A., Zedar, M., Kaats, G., Comings, D. E. (1997). Association of polymorphisms of dopamine D2 receptor (DRD2), and dopamine transporter (DAT1) genes with schizoid/avoidant behaviors (SAB). Mol Psychiatry 2, 239–46.

    Article  PubMed  CAS  Google Scholar 

  • Bodeau-Pean, S., Laurent, C., Campion, D., Jay, M., Thibaut, F., Dollfus, S., Petit, M., Samolyk, D., d’Amato, T., Martinez, M. et al. (1995). No evidence for linkage or association between the dopamine transporter gene and schizophrenia in a French population. Psychiatry Res 59, 1–6.

    Article  PubMed  CAS  Google Scholar 

  • Boykin, M. J., Chetty, C. S., Rajanna, B. (1991). Effects of lead on kinetics of 3H-dopamine uptake by rat brain synaptosomes. Ecotoxicol Environ Saf 22, 88–93.

    Article  PubMed  CAS  Google Scholar 

  • Brockel, B. J., Cory-Slechta, D.A. (1998). Lead, attention, and impulsive behavior: changes in a fixed-ratio waiting-for-reward paradigm. Pharmacol Biochem Behav 60, 545–552.

    Article  PubMed  CAS  Google Scholar 

  • Bruss, M., Porzgen, P., Bryan-Lluka, L. J, Bonisch, H. (1997). The rat norepinephrine transporter: molecular cloning from PC12 cells and functional expression. Brain Res Mol Brain Res 52, 257–62.

    Article  PubMed  CAS  Google Scholar 

  • Carlsson, A. (1987). Perspectives on the discovery of central monoaminergic neurotransmission. Annu Rev Neurosci 10, 19–40.

    Article  PubMed  CAS  Google Scholar 

  • Chiba, K., Trevor, A. J, Castagnoli, N., Jr. (1985). Active uptake of MPP+, a metabolite of MPTP, by brain synaptosomes. Biochem Biophys Res Commun 128, 1228–32.

    Article  PubMed  CAS  Google Scholar 

  • Chinaglia, G., Alvarez, F. J., Probst, A, Palacios, J. M. (1992). Mesostriatal and mesolimbic dopamine uptake binding sites are reduced in Parkinson’ s disease and progressive supranuclear palsy: a quantitative autoradiographic study using [3H]mazindol. Neuroscience 49, 317–27.

    Article  PubMed  CAS  Google Scholar 

  • Ciliax, B. J., Heilman, C., Demchyshyn, L. L., Pristupa, Z. B., Ince, E., Hersch, S. M., Niznik, H. B, Levey, A. I. (1995). The dopamine transporter: immunochemical characterization and localization in brain. J Neurosci 15, 1714–23.

    PubMed  CAS  Google Scholar 

  • Comings, D. E., Wu, S., Chiu, C., Ring, R. H., Gade, R., Ahn, C., MacMurray, J. P., Dietz, G, Muhleman, D. (1996). Polygenic inheritance of Tourette syndrome, stuttering, attention deficit hyperactivity, conduct, and oppositional defiant disorder: the additive and subtractive effect of the three dopaminergic genes-DRD2, D beta H, and DATI. Am J Med Genet 67, 264–88.

    Article  PubMed  CAS  Google Scholar 

  • Cook, E. H., Jr., Stein, M. A., Krasowski, M. D., Cox, N. J., Olkon, D. M., Kieffer, J. E, Leventhal, B. L. (1995). Association of attention-deficit disorder and the dopamine transporter gene. Am J Hum Genet 56, 993–8.

    PubMed  CAS  Google Scholar 

  • Cummings, J. L. (1992). Depression in Parkinson’s disease: a review. American Journal of Psychiatry 149, 443–454.

    PubMed  CAS  Google Scholar 

  • Daniels, A. J. and Reinhard, J. F., Jr. (1988). Energy-driven uptake of the neurotoxin 1-methyl-4phenylpyridinium into chromaffin granules via the catecholamine transporter. J Biol Chem 263, 5034–6.

    PubMed  CAS  Google Scholar 

  • Daniels, G. M. and Amara, S.G. (1999). Regulated Trafficking of the Human Dopamine Transporter. Clatherin-mediated internalization and lysosomal degradation in response to phorbol esters. J. Biol. Chem. 274, 35794–35801.

    Article  PubMed  CAS  Google Scholar 

  • Del Zompo, M., Piccardi, M. P., Ruiu, S., Quartu, M., Gessa, G. L, Vaccari, A. (1993). Selective MPP+ uptake into synaptic dopamine vesicles: passible involvement in MPTP neurotoxicity. Br J Pharmacol 109, 411–4.

    Article  PubMed  Google Scholar 

  • Donovan, D. M., Miner, L.L., Perry, M.P., Revay, R.S., Sharpe, L.G., Przedborski, S., Kostic, V., Philpot, R.M., Kirstein, C.L., Rothman, R.B., Schindler, C.W, UM, G.R. (1999). Cocaine reward and MPTP toxicity: alteration by regional variant dopamine transporter overexpression. Molecular Brain Research 73, 37–49.

    Article  PubMed  CAS  Google Scholar 

  • Edwards, R. H. (1993). Neural degeneration and the transport of neurotransmitters. Ann Neurol 34, 638–45.

    Article  PubMed  CAS  Google Scholar 

  • Erickson, J. D., Eiden, L. E, Hoffman, B. J. (1992). Expression cloning of a reserpine-sensitive vesicular monoamine transporter. Proc Natl Acad Sci U S A 89, 10993–7.

    Article  PubMed  CAS  Google Scholar 

  • Erickson, J. D., Schafer, M. K., Bonner, T. I., Eiden, L. E, Weihe, E. (1996). Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter. Proc Natl Acad Sci USA 93, 5166–71.

    Article  PubMed  CAS  Google Scholar 

  • Fischman, A. J., Babich, J. W., Elmaleh, D. R., Barrow, S. A., Meltzer, P., Hanson, R. N, Madras, B. K. (1997). SPECT imaging of dopamine transporter sites in normal and MPTP-Treated rhesus monkeys. J Nucl Med 38, 144–50.

    PubMed  CAS  Google Scholar 

  • Fischman, A. J., Bonab, A. A., Babich, J. W., Palmer, E. P., Alpert, N. M., Elmaleh, D. R., Callahan, R. J., Barrow, S. A., Graham, W., Meltzer, P. C., Hanson, R. N, Madras, B. K. (1998). Rapid detection of Parkinson’s disease by SPECT with altropane: a selective ligand for dopamine transporters. Synapse 29, 128–41.

    Article  PubMed  CAS  Google Scholar 

  • Fleming, L., Mann, J. B., Bean, J., Briggle, T, Sanchez-Ramos, J. R. (1994). Parkinson’s disease and brain levels of organochlorine pesticides. Ann Neurol 36, 100–3.

    Article  PubMed  CAS  Google Scholar 

  • Fon, E. A., Pothos, E. N., Sun, B. C., Killeen, N., Sulzer, D, Edwards, R. H. (1997). Vesicular transport regulates monoamine storage and release but is not essential for amphetamine action. Neuron 19, 127183.

    Google Scholar 

  • Forno, L. S., DeLanney, L. E., Irwin, I, Langston, J. W. (1993). Similarities and differences between MPTPinduced parkinsonsim and Parkinson’s disease. Neuropathologic considerations. Adv Neurol 60, 600–8.

    PubMed  CAS  Google Scholar 

  • Frey, K. A., Koeppe, R. A., Kilbourn, M. R., Vander Borght, T. M., Albin, R. L., Gilman, S, Kuhl, D. E. (1996). Presynaptic monoaminergic vesicles in Parkinson’s disease and normal aging. Ann Neurol 40, 873–84.

    Article  PubMed  CAS  Google Scholar 

  • Fritz, J. D., Jayanthi, L. D., Thoreson, M. A, Blakely, R. D. (1998). Cloning and chromosomal mapping of the murine norepinephrine transporter. J Neurochem 70, 2241–51.

    Article  PubMed  CAS  Google Scholar 

  • Fumagalli, F., Gainetdinov, R. R., Valenzano, K., Wang, Y. M., Miller, G. W, Caron, M. G. (1999). Increased methamphetamine toxicity in heterozygote VMAT2 knockout mice. J Neuroscience 19, 2424–2431.

    CAS  Google Scholar 

  • Fumagalli, F., Gainetdinov, R. R., Valenzano, K. J, Caron, M. G. (1998). Role of dopamine transporter in methamphetamine-induced neurotoxicity: evidence from mice lacking the transporter. J Neurosci 18, 4861–9.

    PubMed  CAS  Google Scholar 

  • Gainetdinov, R. R., Fumagalli, F., Jones, S. R, Caron, M. G. (1997). Dopamine transporter is required for in vivo MPTP neurotoxicity: evidence from mice lacking the transporter. J Neurochem 69, 1322–5.

    Article  PubMed  CAS  Google Scholar 

  • Gainetdinov, R. R., Fumagalli, F., Wang, Y. M., Jones, S. R., Levey, A. I., Miller, G. W, Caron, M. G. (1998). Increased MPTP neurotoxicity in vesicular monoamine transporter 2 heterozygote knockout mice. J Neurochem 70, 1973–8.

    Article  PubMed  CAS  Google Scholar 

  • Gainetdinov, R. R., Jones, S. R., Fumagalli, F., Wightman, R. M, Caron, M. G. (1998). Re-evaluation of the role of the dopamine transporter in dopamine system homeostasis. Brain Res Brain Res Rev 26, 148–53.

    Article  PubMed  CAS  Google Scholar 

  • Gainetdinov, R. R., Wetsel, W. C., Jones, S. R., Levin, E. D., Jaber, M, Caron, M. G. (1999). Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity. Science 283, 397401.

    Google Scholar 

  • Gelernter, J., Kranzler, H, Lacobelle, J. (1998). Population studies of polymorphisms at loci of neuropsychiatric interest (tryptophan hydroxylase (TPH), dopamine transporter protein (SLC6A3), D3 dopamine receptor (DRD3), apolipoprotein E (APOE), mu opioid receptor (OPRM1), and ciliary neurotrophic factor (CNTF)). Genomics 52, 289–97.

    CAS  Google Scholar 

  • Gelernter, J., Kranzler, H. R., Satel, S. L, Rao, P. A. (1994). Genetic association between dopamine transporter protein alleles and cocaine-induced paranoia. Neuropsychopharmacology 11, 195–200.

    Article  PubMed  CAS  Google Scholar 

  • Gill, M., Daly, G., Heron, S., Hawi, Z, Fitzgerald, M. (1997). Confirmation of association between attention deficit hyperactivity disorder and a dopamine transporter polymorphism. Mol Psychiatry 2, 311–313.

    Article  PubMed  CAS  Google Scholar 

  • Ginovart, N., Lundin, A., Farde, L., Halldin, C., Backman, L., Swahn, C. G., Pauli, S, Sedvall, G. (1997). PET study of the pre-and post-synaptic dopaminergic markers for the neurodegenerative process in Huntington’s disease. Brain 120, 503–14.

    Article  PubMed  Google Scholar 

  • Giovanni, A., Sieber, B. A., Heikkila, R. E, Sonsalla, P. K. (1994a). Studies on species sensitivity to the dopaminergic neurotoxin 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine. Part 1: Systemic administration. J Pharmacol Exp Ther 270, 1000–7.

    PubMed  CAS  Google Scholar 

  • Giovanni, A., Sonsalla, P. K, Heikkila, R. E. (1994b). Studies on species sensitivity to the dopaminergic neurotoxin 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine. Part 2: Central administration of 1methyl-4-phenylpyridinium. J Pharmacol Exp Ther 270, 1008–14.

    PubMed  CAS  Google Scholar 

  • Giros, B. and Caron, M. G. (1993). Molecular characterization of the dopamine transporter. Trends Pharmacol Sci 14, 43–9.

    Article  PubMed  CAS  Google Scholar 

  • Giros, B., el Mestikawy, S., Godinot, N., Zheng, K., Han, H., Yang-Feng, T, Caron, M. G. (1992). Cloning, pharmacological characterization, and chromosome assignment of the human dopamine transporter. Mol Pharmacol 42, 383–90.

    PubMed  CAS  Google Scholar 

  • Giros, B., Jaber, M., Jones, S. R., Wightman, R. M, Caron, M. G. (1996). Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 379, 60612.

    Article  Google Scholar 

  • Gorell, J. M., Johnson, C. C., Rybicki, B. A., Peterson, E. L, Richardson, R. J. (1998). The risk of Parkinson’s disease with exposure to pesticides, farming, well water, and rural living. Neurology 50, 1346–50.

    Article  PubMed  CAS  Google Scholar 

  • Graybiel, A. M., Moratalla, R., Quinn, B., DeLanney, L. E., Irwin, I, Langston, J. W. (1993). Early-stage loss of dopamine uptake-site binding in MPTP-treated monkeys. Adv Neurol 60, 34–9.

    PubMed  CAS  Google Scholar 

  • Hastings, T. G., Lewis, D. A, Zigmond, M. J. (1996). Reactive dopamine metabolites and neurotoxicity: implications for Parkinson’s disease. Adv Exp Med Biol 387, 97–106.

    PubMed  CAS  Google Scholar 

  • Heikkila, R. E., Hess, A, Duvoisin, R. C. (1984). Dopaminergic neurotoxicity of 1-methyl-4-phenyl1,2,5,6- tetrahydropyridine in mice. Science 224, 1451–3.

    Article  PubMed  CAS  Google Scholar 

  • Hersch, S. M., Yi, H., Heilman, C. J., Edwards, R. H, Levey, A. I. (1997). Subcellular localization and molecular topology of the dopamine transporter in the striatum and substantia nigra. J Comp Neurol 388, 211–27.

    Article  PubMed  CAS  Google Scholar 

  • Inada, T., Sugita, T., Dobashi, I., Inagaki, A., Kitao, Y., Matsuda, G., Kato, S., Takano, T., Yagi, G, Asai, M. (1996). Dopamine transporter gene polymorphism and psychiatric symptoms seen in schizophrenic patients at their first episode. Am J Med Genet 67, 406–8.

    Article  PubMed  CAS  Google Scholar 

  • Irwin, 1., DeLanney, L. E., Forno, L. S., Finnegan, K. T., Di Monte, D. A, Langston, J. W. (1990). The evolution of nigrostriatal neurochemical changes in the MPTP- treated squirrel monkey. Brain Res 531, 242–52.

    Article  PubMed  Google Scholar 

  • Javitch, J. A., D’Amato, R. J., Strittmatter, S. M, Snyder, S. H. (1985). Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6–tetrahydropyridine: uptake of the metabolite N-methyl-4phenylpyridine by dopamine neurons explains selective toxicity. Proc Natl Acad Sci U S A 82, 2173–7.

    Article  PubMed  CAS  Google Scholar 

  • Jellinger, K., Linert, L., Kienzl, E., Herlinger, E, Youdim, M. B. (1995). Chemical evidence for 6hydroxydopamine to be an endogenous toxic factor in the pathogenesis of Parkinson’s disease. J Neural Transm Suppl 46, 297–314.

    PubMed  CAS  Google Scholar 

  • Jones, S. R., Bowman, B. P., Kuhn, C. M, Wightman, R. M. (1996). Development of dopamine neurotransmission and uptake inhibition in the caudate nucleus as measured by fast-cyclic voltammetry. Synapse 24, 305–7.

    Article  PubMed  CAS  Google Scholar 

  • Jones, S. R., Gainetdinov, R. R., Jaber, M., Giros, B., Wightman, R. M, Caron, M. G. (1998). Profound neuronal plasticity in response to inactivation of the dopamine transporter. Proc Natl Acad Sci U S A 95, 4029–34.

    Article  PubMed  CAS  Google Scholar 

  • Kawai, H., Makino, Y., Hirobe, M, Ohta, S. (1998). Novel endogenous 1,2,3,4-tetrahydroisoquinoline derivatives: uptake by dopamine transporter and activity to induce parkinsonism. J Neurochem 70, 745–51.

    Article  PubMed  CAS  Google Scholar 

  • Kazumata, K., Dhawan, V., Chaly, T., Antonini, A., Margouleff, C., Belakhlef, A., Neumeyer, J, Eidelberg, D. (1998). Dopamine transporter imaging with fluorine-l8-FPCIT and PET. J Nucl Med 39, 1521–30.

    PubMed  CAS  Google Scholar 

  • King, N., Bassett, A. S., Honer, W. G., Masellis, M, Kennedy, J. L. (1997). Absence of linkage for schizophrenia on the short arm of chromosome 5 in multiplex Canadian families. Am J Med Genet 74, 472–4.

    Article  PubMed  CAS  Google Scholar 

  • Kitayama, S., Shimada, S., Uhl, G. R. (1992). Parkinsonism-inducing neurotoxin MPP+: uptake and toxicity in nonneuronal COS cells expressing dopamine transporter eDNA. Ann Neurol 32, 109–11.

    Article  PubMed  CAS  Google Scholar 

  • Kokkinidis, L. and Anisman, H. (1980). Amphetamine models of paranoid schizophrenia: an overview and elaboration of animal experimentation. Psychol Bull 88, 551–79.

    Article  PubMed  CAS  Google Scholar 

  • Koob, G. F., Rocio, M., Carrera, A., Gold, L. H., Heyser, C. J., Maldonado-Irizarry, C., Markou, A., Parsons, L. H., Roberts, A. J., Schulteis, G., Stinus, L., Walker, J. R., Weissenborn, R, Weiss, F. (1998). Substance dependence as a compulsive behavior. J Psychopharmacol 12, 39–48.

    Article  PubMed  CAS  Google Scholar 

  • Kuhar, M. J. (1992). Molecular pharmacology of cocaine: a dopamine hypothesis and its implications. Ciba Found Symp 166, 81–9.

    PubMed  CAS  Google Scholar 

  • Kuikka, J. T., Tiihonen, J., Bergstrom, K. A., Karhu, J., Rasanen, P, Eronen, M. (1998). Abnormal structure of human striatal dopamine re-uptake sites in habitually violent alcoholic offenders: a fractal analysis [In Process Citation]. Neurosci Lett 253, 195–7.

    Article  PubMed  CAS  Google Scholar 

  • Laakso, A., Bergman, J., Haaparanta, M., Vilkman, H., Solin, O, Hietala, J. (1998). [18F]CFT [(18F)WIN 35,428], a radioligand to study the dopamine transporter with PET: characterization in human subjects. Synapse 28, 244–50.

    Google Scholar 

  • Langston, J. W., Ballard, P., Tetrud, J. W, Irwin, I. (1983). Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219, 979–80.

    Article  PubMed  CAS  Google Scholar 

  • Lesch, K. P., Gross, J., Wolozin, B. L., Franzck, E., Bengel, D., Riederer, P, Murphy, D. L. (1994). Direct sequencing of the reserpine-sensitive vesicular monoamine transporter complementary DNA in unipolar depression and manic depressive illness. Psychiatr Genet 4, 153–160.

    Article  PubMed  CAS  Google Scholar 

  • Liu, Y., Peter, D., Roghani, A., Schuldiner, S., Prive, G. G., Eisenberg, D., Brecha, N, Edwards, R. H. (1992a). A cDNA that suppresses MPP+ toxicity encodes a vesicular amine transporter. Cell 70, 539–51.

    Article  PubMed  CAS  Google Scholar 

  • Liu, Y., Roghani, A, Edwards, R. H. (1992b). Gene transfer of a reserpine-sensitive mechanism of resistance to N- methyl-4-phenylpyridinium. Proc Natl Acad Sci U S A 89, 9074–8.

    Article  PubMed  CAS  Google Scholar 

  • Lucki, I. (1998). The spectrum of behaviors influenced by serotonin. Biol Psychiatry 44, 151–62.

    Article  PubMed  CAS  Google Scholar 

  • Madras, B. K., Meltzer, P. C., Liang, A. Y., Elmaleh, D. R., Babich, J, Fischman, A. J. (1998).

    Google Scholar 

  • Altropane, a SPECT or PET imaging probe for dopamine neurons: I. Dopamine transporter binding in primate brain. Synapse 29, 93–104.

    Google Scholar 

  • Markey, S. P., Johannessen, J. N., Chiueh, C. C., Burns, R. S, Herkenham, M. A. (1984). Intraneuronal generation of a pyridinium metabolite may cause drug-induced parkinsonism. Nature 311, 464–7.

    Article  PubMed  CAS  Google Scholar 

  • Markou, A., Kosten, T. R. and Koob, G. F. (1998). Neurobiological similarities in depression and drug dependence: a self-medication hypothesis. Neuropsychopharmacology 18, 135–74.

    Google Scholar 

  • McKeith, I. G., Perry, E. K, Perry, R. H. (1999). Report of the second dementia with Lewy body international workshop: diagnosis and treatment. Consortium on Dementia with Lewy Bodies. Neurology 53, 902–5.

    Article  PubMed  CAS  Google Scholar 

  • McNaught, K. S., Carrupt, P. A., Altomare, C., Cellamare, S., Carotti, A., Testa, B., Jenner, P, Marsden, C. D. (1998). Isoquinoline derivatives as endogenous neurotoxins in the aetiology of Parkinson’s disease. Biochem Pharmacol 56, 921–33.

    Article  PubMed  CAS  Google Scholar 

  • Miller, G. W., Erickson, J. D., Perez, J. T., Penland, S. N., Mash, D. C., Rye, D. B, Levey, A. I. (1999). Immunochemical analysis of vesicular monoamine transporter (VMAT2) protein in Parkinson’s disease. Experimental Neurology 154, 138–148.

    Article  Google Scholar 

  • Miller, G. W., Gainetdinov, R. R., Levey, A. I, Caron, M. G. (1999). Dopamine transporters and neuronal injury. Trends in Pharmacological Sciences 20, 424–429.

    Article  PubMed  CAS  Google Scholar 

  • Miller, G. W., Gilmor, M. L, Levey, A. I. (1998). Generation of transporter specific antibodies. Methods in Enzymology 296, 407–422.

    Article  PubMed  CAS  Google Scholar 

  • Miller, G. W., Kirby, M. L., Levey, A. I, Bloomquist, J. R. (1999). Heptachlor alters expression and function of dopamine transporters. Neurotoxicology 20, 631–638.

    PubMed  CAS  Google Scholar 

  • Miller, G. W., Staley, J. K., Heilman, C. J., Perez, J. T., Mash, D. C., Rye, D. B, Levey, A. I. (1997). Immunochemical analysis of dopamine transporter protein in Parkinson’s disease. Ann Neurol 4/, 530–9.

    Google Scholar 

  • Moratalla, R., Quinn, B., DeLanney, L. E., Irwin, I., Langston, J. W, Graybiel, A. M. (1992). Differential vulnerability of primate caudate-putamen and striosome-matrix dopamine systems to the neurotoxic effects of 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci U S A 89, 3859–63.

    Article  PubMed  CAS  Google Scholar 

  • Morris, E. D., Babich, J. W., Alpert, N. M., Bonab, A. A., Livni, E., Weise, S., Hsu, H., Christian, B. T., Madras, B. K, Fischman, A. J. (1996). Quantification of dopamine transporter density in monkeys by dynamic PET imaging of multiple injections of 11C-CFT. Synapse 24, 262–72.

    Article  PubMed  CAS  Google Scholar 

  • Naoi, M., Maruyama, W., Kasamatsu, T, Dostert, P. (1998). Oxidation of N-methyl(R)salsolinol: involvement to neurotoxicity and neuroprotection by endogenous catechol isoquinolines. J Neural Transm Suppl 52, 125–38.

    Article  PubMed  CAS  Google Scholar 

  • Patel, A. P., Cerruti, C., Vaughan, R. A, Kuhar, M. J. (1994). Developmentally regulated glycosylation of dopamine transporter. Brain Res Dev Brain Res 83, 53–8.

    Article  PubMed  CAS  Google Scholar 

  • Persico, A. M. and Macciardi, F. (1997). Genotypic association between dopamine transporter gene polymorphisms and schizophrenia. Am J Med Genet 74, 53–7.

    Article  PubMed  CAS  Google Scholar 

  • Peter, D., Liu, Y., Sternini, C., de Giorgio, R., Brecha, N, Edwards, R. H. (1995). Differential expression of two vesicular monoamine transporters. J Neurosci /5, 6179–88.

    Google Scholar 

  • Pifl, C., Giros, B, Caron, M. G. (1993). Dopamine transporter expression confers cytotoxicity to low doses of the parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridinium. J Neurosci 13, 424–653.

    Google Scholar 

  • Pifl, C., Giros, B, Caron, M. G. (1996a). The dopamine transporter. The cloned target site of parkinsonism-inducing toxins and of drugs of abuse. Adv Neurol 69, 235–8.

    PubMed  CAS  Google Scholar 

  • Pifl, C., Hornykiewicz, O., Giros, B, Caron, M. G. (1996b). Catecholamine transporters and 1-methyl-4phenyl-1,2,3,6- tetrahydropyridine neurotoxicity: studies comparing the cloned human noradrenaline and human dopamine transporter. J Pharmacol Exp Ther 277, 1437–43.

    PubMed  CAS  Google Scholar 

  • Popper, C. W. (1997). Antidepressants in the treatment of attention-deficit/hyperactivity disorder. J Clin Psychiatry 58, 14–29; discussion 30–1.

    Google Scholar 

  • Rabey, J. M., Amir, I., Treves, T. A., Oberman, Z, Korczyn, A. D. (1998). Dopamine uptake by platelet storage granules in first-degree relatives of Tourette’s syndrome patients [In Process Citation]. Biol Psychiatry 44, 1166–70.

    Article  PubMed  CAS  Google Scholar 

  • Ramamoorthy, S. and Blakely, R. D. (1999). Phosphorylation and sequestration of serotonin transporters differentially modulated by psychostimulants. Science 285, 763–6.

    Article  PubMed  CAS  Google Scholar 

  • Reinhard, J. F., Jr., Diliberto, E. J., Jr., Viveros, O. H, Daniels, A. J. (1987). Subcellular compartmentalization of 1-methyl-4-phenylpyridinium with catecholamines in adrenal medullary chromaffin vesicles may explain the lack of toxicity to adrenal chromaffin cells. Proc Natl Acad Sci USA 84, 8160–4.

    Google Scholar 

  • Rocha, B. A., Fumagalli, F., Gainetdinov, R. R., Jones, S. R., Ator, R., Giros, B., Miller, G. W, Caron, M. G. (1998). Cocaine self-administration in dopamine transporter knockout mice. Nature Neuroscience 1, 132–137.

    Article  PubMed  CAS  Google Scholar 

  • Sanghera, M. K., Manaye, K., McMahon, A., Sonsalla, P. K, German, D. C. (1997). Dopamine transporter mRNA levels are high in midbrain neurons vulnerable to MPTP. Neuroreport 8, 3327–31.

    Article  PubMed  CAS  Google Scholar 

  • Schuldiner, S., Shirvan, A, Linial, M. (1995). Vesicular neurotransmitter transporters: from bacteria to humans. Physiol Rev 75, 369–92.

    PubMed  CAS  Google Scholar 

  • Shimada, S., Kitayama, S., Lin, C. L., Patel, A., Nanthakumar, E., Gregor, P., Kuhar, M, Uhl, G. (1991). Cloning and expression of a cocaine-sensitive dopamine transporter complementary DNA [published erratum appears in Science 1992 Mar 6;255(5049):1195]. Science 254, 576–8.

    Article  PubMed  CAS  Google Scholar 

  • Shimada, S., Kitayama, S., Walther, D, Uhl, G. (1992). Dopamine transporter mRNA: dense expression in ventral midbrain neurons. Brain Res Mol Brain Res 13, 359–62.

    Article  PubMed  CAS  Google Scholar 

  • Sibley, D. R. (1999). New insights into dopaminergic receptor function using antisense and genetically altered animals [In Process Citation]. Annu Rev Pharmacol Toxicol 39, 313–41.

    Article  PubMed  CAS  Google Scholar 

  • Sibley, D. R., Monsma, F. J., Jr., McVittie, L. D., Gerfen, C. R., Burch, R. M, Mahan, L. C. (1992). Molecular neurobiology of dopamine receptor subtypes. Neurochem Int 20 Suppl, 17S - 22S.

    Google Scholar 

  • Speciale, S. G., Liang, C. L., Sonsalla, P. K., Edwards, R. H, German, D. C. (1998). The neurotoxin 1methyl-4-phenylpyridinium is sequestered within neurons that contain the vesicular monoamine transporter. Neuroscience 84, 1177–85.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi, N., Miner, L. L., Sora, I., Ujike, H., Revay, R. S., Kostic, V., Jackson-Lewis, V., Przedborski, S, Uhl, G. R. (1997). VMAT2 knockout mice: heterozygotes display reduced amphetamine-conditioned reward, enhanced amphetamine locomotion, and enhanced MPTP toxicity. Proc Natl Acad Sci USA 94, 9938–43.

    Article  PubMed  CAS  Google Scholar 

  • Tanner, C. M., Ottman, R., Goldman, S. M., Ellenberg, J., Chan, P., Mayeux, R, Langston, J. W. (1999). Parkinson Disease in Twins. Journal American Medical Association 281, 341–346.

    Article  CAS  Google Scholar 

  • Ueno, S., Nakamura, M., Mikami, M., Kondoh, K., Ishiguro, H., Arinami, T., Komiyama, T., Mitsushio, H., Sano, A, Tanabe, H. (1999). Identification of a novel polymorphism of the human dopamine transporter ( DATI) gene and the significant association with alcoholism. Mol Psychiatry 4, 552–557.

    Google Scholar 

  • Uhl, G. R. (1998). Hypothesis: the role of dopaminergic transporters in selective vulnerability of cells in Parkinson’s disease. Ann Neurol 43, 555–60.

    Article  PubMed  CAS  Google Scholar 

  • Vaccari, A. and Saba, P. (1995). The tyramine-labelled vesicular transporter for dopamine: a putative target of pesticides and neurotoxins. Eur J Pharmacol 292, 309–14.

    PubMed  CAS  Google Scholar 

  • Waldman, I. D., Rowe, D. C., Abramowitz, A., Kozel, S. T., Mohr, J. H., Sherman, S. L., Cleveland, H. H., Sanders, M. L., Gard, J. M, Stever, C. (1998). Association and Linkage of the Dopamine Transporter Gene and Attention- Deficit Hyperactivity Disorder in Children: Heterogeneity owing to Diagnostic Subtype and Severity. Am J Hum Genet 63, 1767–1776.

    Article  PubMed  CAS  Google Scholar 

  • Wang, Y. M., Gainetdinov, R. R., Fumagalli, F., Xu, F., Jones, S. R., Bock, C. B., Miller, G. W., Wightman, R. M, Caron, M. G. (1997). Knockout of the vesicular monoamine transporter 2 gene results in neonatal death and supersensitivity to cocaine and amphetamine. Neuron 19, 1285–96.

    Article  PubMed  CAS  Google Scholar 

  • Wellington, C. L., Brinkman, R. R., O’Kusky, J. R, Hayden, M. R. (1997). Toward understanding the molecular pathology of Huntington’s disease. Brain Pathol 7, 979–1002.

    Article  PubMed  CAS  Google Scholar 

  • Wilson, J. M., Kalasinsky, K. S., Levey, A. I., Bergeron, C., Reiber, G., Anthony, R. M., Schmunk, G. A., Shannak, K., Haycock, J. W, Kish, S. J. (1996a). Striatal dopamine nerve terminal markers in human, chronic methamphetamine users. Nat Med 2, 699–703.

    Article  PubMed  CAS  Google Scholar 

  • Wilson, J. M., Levey, A. I., Bergeron, C., Kalasinsky, K., Ang, L., Peretti, F., Adams, V. I., Smialek, J., Anderson, W. R., Shannak, K., Deck, J., Niznik, H. B, Kish, S. J. (1996b). Striatal dopamine, dopamine transporter, and vesicular monoamine transporter in chronic cocaine users. Ann Neurol 40, 428–39.

    Article  PubMed  CAS  Google Scholar 

  • Wilson, J. M., Levey, A. I., Rajput, A., Ang, L., Guttman, M., Shannak, K., Niznik, H. B., Hornykiewicz, O., Pifl, C., Kish, S. J. (1996c). Differential changes in neurochemical markers of striatal dopamine nerve terminals in idiopathic Parkinson’s disease. Neurology 47, 718–26.

    Article  PubMed  CAS  Google Scholar 

  • Yelin, R. and Schuldiner, S. (1995). The pharmacological profile of the vesicular monoamine transporter resembles that of multidrug transporters. FEBS Lett 377, 201–7.

    Article  PubMed  CAS  Google Scholar 

  • Zuddas, A., Fascetti, F., Corsini, G. U, Piccardi, M. P. (1994). In brown Norway rats, MPP+ is accumulated in the nigrostriatal dopaminergic terminals but it is not neurotoxic: a model of natural resistance to MPTP toxicity. Exp Neurol 127, 54–61.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Gary W. Miller
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  2. Raul R. Gainetdinov
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  3. Marc G. Caron
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Editors and Affiliations

  1. Psychobiology Research Unit, Department of Psychology, Tel Aviv University, 69978, Tel-Aviv, Israel

    Michael S. Myslobodsky

  2. Howard University, USA

    Michael S. Myslobodsky

  3. Department of Psychology, Tel Aviv University, 69978, Tel-Aviv, Israel

    Ina Weiner

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Miller, G.W., Gainetdinov, R.R., Caron, M.G. (2000). Involvement of Dopamine Transporters in Psychiatric Disorders. In: Myslobodsky, M.S., Weiner, I. (eds) Contemporary Issues in Modeling Psychopathology. Neurobiological Foundation of Aberrant Behaviors, vol 1. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-4860-4_1

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  • DOI: https://doi.org/10.1007/978-1-4757-4860-4_1

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