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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
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.
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.
Ben-Shachar, D., Zuk, R., Glinka, Y. (1995). Dopamine neurotoxicity: inhibition of mitochondrial respiration. J Neurochem 64, 718–23.
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.
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.
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.
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.
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.
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.
Carlsson, A. (1987). Perspectives on the discovery of central monoaminergic neurotransmission. Annu Rev Neurosci 10, 19–40.
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.
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.
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.
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.
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.
Cummings, J. L. (1992). Depression in Parkinson’s disease: a review. American Journal of Psychiatry 149, 443–454.
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.
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.
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.
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.
Edwards, R. H. (1993). Neural degeneration and the transport of neurotransmitters. Ann Neurol 34, 638–45.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Giros, B. and Caron, M. G. (1993). Molecular characterization of the dopamine transporter. Trends Pharmacol Sci 14, 43–9.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Kokkinidis, L. and Anisman, H. (1980). Amphetamine models of paranoid schizophrenia: an overview and elaboration of animal experimentation. Psychol Bull 88, 551–79.
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.
Kuhar, M. J. (1992). Molecular pharmacology of cocaine: a dopamine hypothesis and its implications. Ciba Found Symp 166, 81–9.
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.
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.
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.
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.
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.
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.
Lucki, I. (1998). The spectrum of behaviors influenced by serotonin. Biol Psychiatry 44, 151–62.
Madras, B. K., Meltzer, P. C., Liang, A. Y., Elmaleh, D. R., Babich, J, Fischman, A. J. (1998).
Altropane, a SPECT or PET imaging probe for dopamine neurons: I. Dopamine transporter binding in primate brain. Synapse 29, 93–104.
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.
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.
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.
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.
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.
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.
Miller, G. W., Gilmor, M. L, Levey, A. I. (1998). Generation of transporter specific antibodies. Methods in Enzymology 296, 407–422.
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.
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.
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.
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.
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.
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.
Persico, A. M. and Macciardi, F. (1997). Genotypic association between dopamine transporter gene polymorphisms and schizophrenia. Am J Med Genet 74, 53–7.
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.
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.
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.
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.
Popper, C. W. (1997). Antidepressants in the treatment of attention-deficit/hyperactivity disorder. J Clin Psychiatry 58, 14–29; discussion 30–1.
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.
Ramamoorthy, S. and Blakely, R. D. (1999). Phosphorylation and sequestration of serotonin transporters differentially modulated by psychostimulants. Science 285, 763–6.
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.
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.
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.
Schuldiner, S., Shirvan, A, Linial, M. (1995). Vesicular neurotransmitter transporters: from bacteria to humans. Physiol Rev 75, 369–92.
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.
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.
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.
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.
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.
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.
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.
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.
Uhl, G. R. (1998). Hypothesis: the role of dopaminergic transporters in selective vulnerability of cells in Parkinson’s disease. Ann Neurol 43, 555–60.
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.
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.
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.
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.
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.
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.
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.
Yelin, R. and Schuldiner, S. (1995). The pharmacological profile of the vesicular monoamine transporter resembles that of multidrug transporters. FEBS Lett 377, 201–7.
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.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Springer Science+Business Media New York
About this chapter
Cite this chapter
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
Download citation
DOI: https://doi.org/10.1007/978-1-4757-4860-4_1
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4419-4996-7
Online ISBN: 978-1-4757-4860-4
eBook Packages: Springer Book Archive