Altered midbrain dopaminergic neurotransmission during development in an animal model of ADHD
Abstract
To understand the onset and the molecular mechanisms triggering dopaminergic (DA) dysregulation in Attention-Deficit Hyperactivity Disorder (ADHD), we have used the Spontaneously Hypertensive Rats (SHR), the most widely studied animal model for this disease. We have studied the pattern of expression of specific genes involved in DA neuron differentiation, survival and function during postnatal (P) development of the ventral midbrain in SHR males. Our results show that tyrosine hydroxylase and DA transporter gene expression are significantly and transiently reduced in the SHR midbrain during the first month of postnatal development, although with a different kinetic. The other genes analyzed do not show significant variation between SHR and control rats. In addition, high-affinity DA uptake activity is significantly reduced in synaptosomes obtained from the striatum of 1-month-old SHR, when compared to controls. Our data suggest that down-regulation of DA neurotransmission occurs in the midbrain of SHR in a developmentally regulated temporal window during postnatal development, thus strengthening the hypodopaminergic hypothesis in the pathogenesis of ADHD.
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DAT gene expression is transiently reduced in the SHR midbrain during the first month after birth, and increased in adult SHR compared with controls, resulting in abnormal mesostriatal DA transmission during postnatal development and possibly adulthood.
“DAT gene expression is transiently reduced in the SHR midbrain during the first month after birth, and increased in adult SHR compared with controls [457], which results in abnormal mesostriatal DA transmission in the rats during postnatal development, and possibly in adulthood [458].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [458]
Cites
Dopamine receptors: from structure to function
MISSALE, C., NASH, S. R., ROBINSON, S. W., JABER, M., & CARON, M. G. (1998) · Physiological Reviews · doi:10.1152/physrev.1998.78.1.189 · Cited by 3,633 · see citing works
Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter
Giros, B., Jaber, M., Jones, S. R., Wightman, R. M., & Caron, M. G. (1996) · Nature · doi:10.1038/379606a0 · Cited by 2,476 · see citing works
Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes
Castellanos, F. X., & Tannock, R. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn896 · Cited by 1,827 · see citing works
Dopamine Neuron Agenesis in Nurr1-Deficient Mice
Zetterström, R. H., Solomin, L., Jansson, L., Hoffer, B. J., Olson, L., & Perlmann, T. (1997) · Science · doi:10.1126/science.276.5310.248 · Cited by 1,096 · see citing works
Role of Serotonin in the Paradoxical Calming Effect of Psychostimulants on Hyperactivity
Gainetdinov, R. R., Wetsel, W. C., Jones, S. R., Levin, E. D., Jaber, M., & Caron, M. G. (1999) · Science · doi:10.1126/science.283.5400.397 · Cited by 885 · see citing works
Cárdenas, O. S., Quintana-Hau, J. D. D., Le, W., Smidt, M. P., Cox, J. J., Mayo, F. J. D., Burbach, J. P. H., & Conneely, O. M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.4013 · Cited by 744 · see citing works
Intricate Regulation of Tyrosine Hydroxylase Activity and Gene Expression
Kumer, S. C., & Vrana, K. E. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.67020443.x · Cited by 680 · see citing works
Solanto, M. V. (1998) · Behavioural Brain Research · doi:10.1016/s0166-4328(97)00175-7 · Cited by 677 · see citing works
Mechanisms of Amphetamine Action Revealed in Mice Lacking the Dopamine Transporter
Jones, S. R., Gainetdinov, R. R., Wightman, R. M., & Caron, M. G. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-06-01979.1998 · Cited by 626 · see citing works
Attention-deficit hyperactivity disorder and hyperkinetic disorder
Jm, S., Sergeant, J. A., Taylor, E. A., Sonuga-Barke, E. J. S., Jensen, P. S., & Dp, C. (1998) · The Lancet · doi:10.1016/s0140-6736(97)11450-7 · Cited by 602 · see citing works
Attention-deficit hyperactivity disorder and hyperkinetic disorder
Swanson, J. M., Sergeant, J. A., Taylor, E., Sonuga-Barke, E. J. S., Jensen, P. S., & Cantwell, D. P. (2001) · Routledge eBooks · doi:10.4324/9781315054315-2 · Cited by 573 · see citing works
Sagvolden, T. (2000) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(99)00058-5 · Cited by 525 · see citing works
Krause, K.-H., Dresel, S. H., Krause, J., Kung, H. F., & Tatsch, K. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01040-5 · Cited by 521 · see citing works
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. C., & Stever, C. (1998) · The American Journal of Human Genetics · doi:10.1086/302132 · Cited by 462 · see citing works
Dopamine dysfunction in AD/HD: integrating clinical and basic neuroscience research
Solanto, M. V. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(01)00431-4 · Cited by 456 · see citing works
Swanson, J. M., Flodman, P. L., Kennedy, J., Spence, M. A., Moyzis, R. K., Schuck, S. E. B., Murias, M., Moriarity, J., Barr, C. L., Smith, M., et al. (2000) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(99)00062-7 · Cited by 448 · see citing works
Saunders, C., Ferrer, J. V., Shi, L., Chen, J., Merrill, G. A., Lamb, M. E., Leeb-Lundberg, L. M. F., Carvelli, L., Javitch, J. A., & Galli, A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.110035297 · Cited by 410 · see citing works
Specification of catecholaminergic and serotonergic neurons
Goridis, C., & Rohrer, H. (2002) · Nature reviews. Neuroscience · doi:10.1038/nrn871 · Cited by 350 · see citing works
Zetterström, R. H., Williams, R., Perlmann, T., & Olson, L. (1996) · Molecular Brain Research · doi:10.1016/0169-328x(96)00074-5 · Cited by 340 · see citing works
Volkow, N. D., Wang, G., Fowler, J. S., Logan, J., Franceschi, D., Maynard, L., Ding, Y., Gatley, S. J., Gifford, A., Zhu, W., et al. (2002) · Synapse · doi:10.1002/syn.10038 · Cited by 321 · see citing works
Castillo, S. O., Baffi, J., Palkovits, M., Goldstein, D. S., Kopin, I. J., Witta, J., Magnuson, M. A., & Nikodem, V. M. (1998) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.1998.0673 · Cited by 292 · see citing works
Elsworth, J. D., & Roth, R. H. (1997) · Experimental Neurology · doi:10.1006/exnr.1996.6379 · Cited by 282 · see citing works
Dresel, S., Krause, J., Krause, K.-H., LaFougere, C., Brinkbäumer, K., Kung, H. F., Hahn, K., & Tatsch, K. (2000) · European Journal of Nuclear Medicine · doi:10.1007/s002590000330 · Cited by 278 · see citing works
Cognitive neuroscience of attention deficit hyperactivity disorder and hyperkinetic disorder
Swanson, J. M., Castellanos, F. X., Murias, M., LaHoste, G. J., & Kennedy, J. L. (1998) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(98)80150-5 · Cited by 272 · see citing works
Animal models of attention-deficit hyperactivity disorder.
Davids, E., Zhang, K., Tarazi, F. I., & Baldessarini, R. J. (2003) · Brain Research Reviews · doi:10.1016/s0165-0173(02)00274-6 · Cited by 250 · see citing works
Loss of autoreceptor functions in mice lacking the dopamine transporter
Jones, S. R., Gainetdinov, R. R., Hu, X., Cooper, D., Wightman, R. M., White, F. J., & Caron, M. G. (1999) · Nature Neuroscience · doi:10.1038/10204 · Cited by 247 · see citing works
Fate of Mesencephalic AHD2-Expressing Dopamine Progenitor Cells in Nurr1 Mutant Mice
Wallén, Å., Zetterström, R. H., Solomin, L., Arvidsson, M., Olson, L., & Perlmann, T. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4691 · Cited by 232 · see citing works
Dopaminergic System Genes in ADHD: Toward a Biological Hypothesis
Kirley, A., Hawi, Z., Daly, G., McCarron, M., Mullins, C., Millar, N., Waldman, I., Fitzgerald, M., & Gill, M. (2002) · Neuropsychopharmacology · doi:10.1016/s0893-133x(02)00315-9 · Cited by 225 · see citing works
Dynamics of tyrosine hydroxylase promoter activity during midbrain dopaminergic neuron development
Matsushita, N., Okada, H., Yasoshima, Y., TAKAHASHI, K. W., Kiuchi, K., & Kobayashi, K. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00972.x · Cited by 212 · see citing works
Mercuri, N. B., Saiardi, A., Bonci, A., Picetti, R., Calabresi, P., Bernardi, G., & Borrelli, E. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00135-8 · Cited by 198 · see citing works
Current concepts on the neurobiology of Attention-Deficit/Hyperactivity Disorder
Biederman, J., & Faraone, S. V. (2002) · Journal of Attention Disorders · doi:10.1177/070674370200601s03 · Cited by 192 · see citing works
Le, W. D., Conneely, O. M., He, Y., Jankovic, J. J., & Appel, S. H. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.02218.x · Cited by 187 · see citing works
Swanson, J. M., & Volkow, N. D. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(01)00433-8 · Cited by 173 · see citing works
Russell, V. A. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(01)00425-9 · Cited by 167 · see citing works
Russell, V. A., de Villiers, A. S., Sagvolden, T., Lamm, M. C. L., & Taljaard, J. J. F. (1998) · Behavioural Brain Research · doi:10.1016/s0166-4328(97)00177-0 · Cited by 147 · see citing works
Pharmacology and regulation of the neuronal dopamine transporter
Reith, M. E. A., Xu, C., & Chen, N. (1997) · European Journal of Pharmacology · doi:10.1016/s0014-2999(97)00065-4 · Cited by 143 · see citing works
Berger, D. F., & Sagvolden, T. (1998) · Behavioural Brain Research · doi:10.1016/s0166-4328(97)00171-x · Cited by 123 · see citing works
A Critique of Current Diagnostic Criteria for Attention Deficit Hyperactivity Disorder
Barkley, R. A. (1990) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/00004703-199012000-00014 · Cited by 120 · see citing works
Association of homozygous 7048G7049 variant in the intron six of Nurr1 gene with Parkinson’s disease
Xu, P., Liang, R., Jankovic, J. J., Hunter, C., Zeng, Y.-X., Ashizawa, T., Lai, D., & Le, W. (2002) · Neurology · doi:10.1212/wnl.58.6.881 · Cited by 118 · see citing works
Ueno, K., Togashi, H., Mori, K., Matsumoto, M., Ohashi, S., Hoshino, A., Fujita, T., Saito, H., Minami, M., & Yoshioka, M. (2002) · Behavioural Pharmacology · doi:10.1097/00008877-200202000-00001 · Cited by 116 · see citing works
Xiao, Q., Castillo, S. O., & Nikodem, V. M. (1996) · Neuroscience · doi:10.1016/0306-4522(96)00159-5 · Cited by 114 · see citing works
Trinh, J. V., Nehrenberg, D. L., Jacobsen, J. P. R., Caron, M. G., & Wetsel, W. C. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00165-9 · Cited by 113 · see citing works
Decreased expression of the transcription factor NURR1 in dopamine neurons of cocaine abusers
Bannon, M. J., Pruetz, B., Manning-Bog, A., Whitty, C. J., Michelhaugh, S. K., Sacchetti, P., Granneman, J. G., Mash, D. C., & Schmidt, C. J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.092654299 · Cited by 109 · see citing works
Barkley, R. A. (1990) · PubMed · Cited by 108 · see citing works
Comparative distribution of NURR1 and NUR77 nuclear receptors in the mouse central nervous system
Cárdenas, O. S., & Conneely, O. M. (1996) · Journal of Molecular Neuroscience · doi:10.1007/bf02736848 · Cited by 106 · see citing works
Carey, M. P., Diewald, L., Esposito, F., Pellicano, M. P., Carnevale, U. A. G., Sergeant, J. A., Papa, M., & Sadile, A. G. (1998) · Behavioural Brain Research · doi:10.1016/s0166-4328(97)00178-2 · Cited by 94 · see citing works
Eells, J. B., Lipska, B. K., Yeung, S. K., Misler, J. A., & Nikodem, V. M. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(02)00185-7 · Cited by 92 · see citing works
Genetic influences on attention deficit hyperactivity disorder
Faraone, S. V., & Doyle, A. E. (2000) · Current Psychiatry Reports · doi:10.1007/s11920-000-0059-6 · Cited by 89 · see citing works
Otter, I., Conus, S., Ravn, U., et al. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.11.6110 · Cited by 89 · see citing works
Gonadal hormones and the induction of intraspecific fighting in mice
Gandelman, R. J. (1980) · Neuroscience & Biobehavioral Reviews · doi:10.1016/0149-7634(80)90011-1 · Cited by 87 · see citing works
Russell, V. A. (2000) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(99)00056-1 · Cited by 86 · see citing works
Genetic and epigenetic control of midbrain dopaminergic neuron development
Perrone‐Capano, C., & di Porzio, U. (2000) · The International Journal of Developmental Biology · doi:10.1387/ijdb.11061432 · Cited by 75 · see citing works
Self-citationPernas-Alonso, R., Morelli, F., di Porzio, U., & Perrone‐Capano, C. (1999) · Brain Research Protocols · doi:10.1016/s1385-299x(99)00045-8 · Cited by 69 · see citing works
Self-citationSteel, M. C., & Buckley, N. J. (1993) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)13644-4 · Cited by 65 · see citing works
Dopamine Synthesis Precedes Dopamine Uptake in Embryonic Rat Mesencephalic Neurons
Fiszman, M. L., Zuddas, A., Masana, M. I., Barker, J. L., & di Porzio, U. (1991) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1991.tb08164.x · Cited by 54 · see citing works
Apoptotic genes expression in the lumbar dorsal horn in a model neuropathic pain in rat
Maione, S., Siniscalco, D., Galderisi, U., et al. (2002) · Neuroreport · doi:10.1097/00001756-200201210-00024 · Cited by 49 · see citing works
Papa, M., Diewald, L., Carey, M. P., Esposito, F., Carnevale, U. A. G., & Sadile, A. G. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(01)00421-1 · Cited by 49 · see citing works
Specific Reinnervation of Lesioned Mouse Striatum by Grafted Mesencephalic Dopaminergic Neurons
Zuddas, A., Corsini, G. U., Barker, J. L., Kopin, I. J., & di Porzio, U. (1991) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1991.tb00813.x · Cited by 45 · see citing works
Activity, non-selective attention and emotionality in dopamine D2/D3 receptor knock-out mice
Vallone, D., Pignatelli, M., Grammatikopoulos, G., Ruocco, L. A., Bozzi, Y., Westphal, H., Borrelli, E., & Sadile, A. G. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(01)00428-4 · Cited by 41 · see citing works
Target cells modulate dopamine transporter gene expression during brain development
Perrone‐Capano, C., Tino, A., & di Porzio, U. (1994) · Neuroreport · doi:10.1097/00001756-199405000-00031 · Cited by 39 · see citing works
Self-citationCross-sensitization between cocaine and GBR 12909, a dopamine uptake inhibitor
Baldo, B. A., & Kelley, A. E. (1991) · Brain Research Bulletin · doi:10.1016/0361-9230(91)90289-v · Cited by 30 · see citing works
Epigenetic cues in midbrain dopaminergic neuron development
Perrone‐Capano, C., Pozzo, P. D., & di Porzio, U. (2000) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(99)00054-8 · Cited by 26 · see citing works
Self-citationEpigenetic factors and midbrain dopaminergic neurone development
Perrone‐Capano, C., & di Porzio, U. (1996) · BioEssays · doi:10.1002/bies.950181008 · Cited by 17 · see citing works
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- Authors
- Leo, D., Sorrentino, E., Volpicelli, F., Eyman, M., Greco, D., Viggiano, D., di Porzio, U., & Perrone-Capano, C.
- Affiliations
- Institute of Genetics and Biophysics (IT)
- University of Naples Federico II (IT)
- University of Campania "Luigi Vanvitelli" (IT)
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2003-11
- Volume
- 27
- Issue
- 7
- Pages
- 661-669
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W1971910459
- Cited by
- 103
- References
- 63
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 5 · 2016: 2 · 2015: 2 · 2014: 5 · 2013: 5 · 2012: 8
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- attention deficit hyperactivity disorder, midbrain dopaminergic neurons, spontaneously hypertensive rats, animal model of ADHD, postnatal development, tyrosine hydroxylase, dopamine transporter, dopamine signaling, gene expression
- MeSH terms
- Animals, Attention Deficit Disorder with Hyperactivity, Brain Chemistry, Cell Differentiation, Disease Models, Animal, Dopamine, Male, Mesencephalon, Synaptic Transmission, Neurons, Rats, Inbred SHR, Rats, Inbred WKY, Down-Regulation, Gene Expression Regulation, Developmental, Rats
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