Age-related reduction in dopamine D1 receptors in the human brain: From late childhood to adulthood, a positron emission tomography study
Abstract
Age-dependent decrease in dopamine receptor density throughout adulthood is well described, meanwhile less is known about development of dopamine system in humans and in vivo it has not been investigated. We examined dopamine D1 receptor (D1DR) binding in the cerebral cortex and striatum of 12 adolescents (mean age 13.5+/-1.8 years) and 18 young adults (25+/-2.3 years) using positron emission tomography (PET) and radioligand [(11)C]SCH23390. Over the age span of 10-30 years [(11)C]SCH23390 binding (binding potential, BP) declined in all brain regions. The rate of BP decline was age-segment and brain region dependent. Most pronounced decline in BP was observed in the cortical regions during adolescence (mean BP in adults lower by 14-26% as compared to adolescents, P<0.0001). Significantly slower rate of decline in BP was observed in two cortical regions (orbitofrontal and posterior cingulate cortices) and striatal regions. The present PET-study provides new evidence on the development of D1DR in humans in vivo which is of critical importance for understanding of the biology of neurodevelopmental disorders.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the living human brain, D1 receptor binding decreases in the PFC and parietal cortex over age 10 to 30 years.
“In the living brain, a decrease in D1 receptor binding was observed in the PFC and parietal cortex over an age span of 10 to 30 years (34).”
From Influence of the COMT genotype on working memory and brain activity changes during development (2011) · cites this paper as [34]
Cites
Brain development during childhood and adolescence: a longitudinal MRI study
Giedd, J. N., Blumenthal, J., Jeffries, N. O., Castellanos, F. X., Liu, H., Zijdenbos, A., Paus, T., Evans, A. C., & Rapoport, J. L. (1999) · Nature Neuroscience · doi:10.1038/13158 · Cited by 5,552 · see citing works
Implications of Normal Brain Development for the Pathogenesis of Schizophrenia
Weinberger, D. R. (1987) · Archives of General Psychiatry · doi:10.1001/archpsyc.1987.01800190080012 · Cited by 3,724 · see citing works
Synaptic density in human frontal cortex —Developmental changes and effects of aging
Peter R., H. (1979) · Brain Research · doi:10.1016/0006-8993(79)90349-4 · Cited by 2,645 · see citing works
Simplified Reference Tissue Model for PET Receptor Studies
Lammertsma, A. A., & Hume, S. P. (1996) · NeuroImage · doi:10.1006/nimg.1996.0066 · Cited by 2,025 · see citing works
Neurodevelopmental Trajectories of the Human Cerebral Cortex
Shaw, P., Kabani, N. J., Lerch, J. P., Eckstrand, K., Lenroot, R., Gogtay, N., Greenstein, D., Clasen, L., Evans, A., Rapoport, J. L., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.5309-07.2008 · Cited by 1,644 · see citing works
Schizophrenia: Caused by a fault in programmed synaptic elimination during adolescence?
Feinberg, I. (1982) · Journal of Psychiatric Research · doi:10.1016/0022-3956(82)90038-3 · Cited by 1,395 · see citing works
Life and Death of Neurons in the Aging Brain
Morrison, J. H., & Hof, P. R. (1997) · Science · doi:10.1126/science.278.5337.412 · Cited by 1,344 · see citing works
Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex
Rakic, P., Bourgeois, J.-P., Eckenhoff, M. F., Zecevic, N., & Goldman-Rakic, P. S. (1986) · Science · doi:10.1126/science.3952506 · Cited by 1,133 · see citing works
Sowell, E. R., Thompson, P. M., Tessner, K. D., & Toga, A. W. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-22-08819.2001 · Cited by 983 · see citing works
The teen brain: insights from neuroimaging
Giedd, J. N. (2008) · Journal of Adolescent Health · doi:10.1016/j.jadohealth.2008.01.007 · Cited by 775 · see citing works
SCH 23390—The first selective dopamine D-1 antagonist
Hyttel, J. (1983) · European Journal of Pharmacology · doi:10.1016/0014-2999(83)90381-3 · Cited by 740 · see citing works
Prefrontal Dopamine D<sub>1</sub>Receptors and Working Memory in Schizophrenia
Abi-Dargham, A., Mawlawi, O., Lombardo, I., Gil, R., Martinez, D., Huang, Y., Hwang, D.-R., Keilp, J., Kochan, L., Van Heertum, R., et al. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-09-03708.2002 · Cited by 724 · see citing works
Klingberg, T., Forssberg, H., & Westerberg, H. (2002) · Journal of Cognitive Neuroscience · doi:10.1162/089892902317205276 · Cited by 695 · see citing works
Self-citationGenes, dopamine and cortical signal-to-noise ratio in schizophrenia
Winterer, G., & Weinberger, D. R. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.08.002 · Cited by 598 · see citing works
A Critical Period of Brain Development: Studies of Cerebral Glucose Utilization with PET
Chugani, H. T. (1998) · Preventive Medicine · doi:10.1006/pmed.1998.0274 · Cited by 590 · see citing works
A Developmental fMRI Study of the Stroop Color-Word Task
Adleman, N. E., Menon, V., Blasey, C. M., White, C. D., Warsofsky, I. S., Glover, G. H., & Reiss, A. L. (2002) · NeuroImage · doi:10.1006/nimg.2001.1046 · Cited by 569 · see citing works
Wienhard, K., Dahlbom, M. L., Eriksson, L., Michel, C. J., Bruckbauer, T., Pietrzyk, U., & Heiss, W. (1994) · Journal of Computer Assisted Tomography · doi:10.1097/00004728-199401000-00023 · Cited by 561 · see citing works
Changes in cortical dopamine D1 receptor binding associated with cognitive training
McNab, F., Varrone, A., Farde, L., Jucaite, A., Bystritsky, P., Forssberg, H., & Klingberg, T. (2009) · Science · doi:10.1126/science.1166102 · Cited by 545 · see citing works
Self-citationTeicher, M. H., Andersen, S. L., & Hostetter, J. C. (1995) · Developmental Brain Research · doi:10.1016/0165-3806(95)00109-q · Cited by 505 · see citing works
Distribution of D1- and D2-Dopamine Receptors, and Dopamine and Its Metabolites in the Human Brain
Hall, H., Sedvall, G., Magnusson, O., Kopp, J., Halldin, C., & Farde, L. (1994) · Neuropsychopharmacology · doi:10.1038/sj.npp.1380111 · Cited by 441 · see citing works
Self-citationHuman brain dopamine receptors in children and aging adults
Seeman, P., Bzowej, N. H., Guan, H. ‐., Bergeron, C., Becker, L. E., Reynolds, G. P., Bird, E. D., Riederer, P., Jellinger, K., Watanabe, S., et al. (1987) · Synapse · doi:10.1002/syn.890010503 · Cited by 404 · see citing works
Lidow, M. S., Goldman-Rakic, P. S., Gallager, D. W., & Rakic, P. (1991) · Neuroscience · doi:10.1016/0306-4522(91)90003-7 · Cited by 394 · see citing works
Cyclic cortical reorganization during early childhood
Thatcher, R. W. (1992) · Brain and Cognition · doi:10.1016/0278-2626(92)90060-y · Cited by 387 · see citing works
Smiley, J. F., Levey, A. I., Ciliax, B. J., & Goldman‐Rakic, P. S. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.12.5720 · Cited by 383 · see citing works
Neural development of selective attention and response inhibition
Booth, J. R., Burman, D. D., Meyer, J. R., Lei, Z., Trommer, B. L., Davenport, N. D., Li, W., Parrish, T. B., Gitelman, D. R., & Mesulam, M. M. (2003) · NeuroImage · doi:10.1016/s1053-8119(03)00404-x · Cited by 366 · see citing works
Tarazi, F. I., & Baldessarini, R. J. (2000) · International Journal of Developmental Neuroscience · doi:10.1016/s0736-5748(99)00108-2 · Cited by 327 · see citing works
m, M. B., thius, J. B., Eriksson, L., Greitz, T. V. B., Ribbe, T., & Wid�n, L. (1981) · Journal of Computer Assisted Tomography · doi:10.1097/00004728-198102000-00027 · Cited by 315 · see citing works
Striatal dopamine deficiency in parkinson's disease: Role of aging
Scherman, D., Desnos, C., Darchen, F., Pollak, P., Javoy-Agid, F., & Agid, Y. (1989) · Annals of Neurology · doi:10.1002/ana.410260409 · Cited by 284 · see citing works
PET analysis of human dopamine receptor subtypes using 11C-SCH 23390 and 11C-raclopride
Farde, L., Halldin, C., Stone‐Elander, S., & Sedvall, G. (1987) · Psychopharmacology · doi:10.1007/bf00210831 · Cited by 283 · see citing works
Self-citationChanges in synaptic density in motor cortex of rhesus monkey during fetal and postnatal life
Zecevic, N., Bourgeois, J.-P., & Rakic, P. (1989) · Developmental Brain Research · doi:10.1016/0165-3806(89)90124-7 · Cited by 253 · see citing works
Santana, N., Mengod, G., & Artigas, F. (2009) · Cerebral Cortex · doi:10.1093/cercor/bhn134 · Cited by 231 · see citing works
A central role for Necl4 (SynCAM4) in Schwann cell–axon interaction and myelination
Spiegel, I., Adamsky, K., Eshed, Y., Milo, R., Sabanay, H., Sarig-Nadir, O., Horresh, I., Scherer, S. S., Rasband, M. N., & Peles, E. (2007) · Nature Neuroscience · doi:10.1038/nn1915 · Cited by 226 · see citing works
Age-related changes in human D1 dopamine receptors measured by positron emission tomography
Suhara, T., Fukuda, H., Inoue, O., Itoh, T., Suzuki, K., Yamasaki, T., & Tateno, Y. (1991) · Psychopharmacology · doi:10.1007/bf02244071 · Cited by 212 · see citing works
SCH 23390: The First Selective Dopamine D1‐Like Receptor Antagonist
Bourne, J. A. (2001) · CNS Drug Reviews · doi:10.1111/j.1527-3458.2001.tb00207.x · Cited by 196 · see citing works
Haycock, J. W., Becker, L. E., Ang, L. C., Furukawa, Y., Hornykiewicz, O., & Kish, S. J. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02017.x · Cited by 195 · see citing works
Age-dependent decline in human brain dopamine D1 and D2 receptors
Rinne, J. O., Lönnberg, P., & Marjamäki, P. (1990) · Brain Research · doi:10.1016/0006-8993(90)90423-9 · Cited by 192 · see citing works
Dopamine receptors in human brain: Autoradiographic distribution of D1 sites
Cortés, R., Gueye, B., Pazos, Á., Probst, A., & Palacios, J. M. (1989) · Neuroscience · doi:10.1016/0306-4522(89)90178-4 · Cited by 190 · see citing works
Halldin, C., Stone‐Elander, S., Farde, L., et al. (1986) · International Journal of Radiation Applications and Instrumentation Part A Applied Radiation and Isotopes · doi:10.1016/0883-2889(86)90044-4 · Cited by 175 · see citing works
Self-citationPET Study of D1 Dopamine Receptor Binding in Neuroleptic-Naive Patients With Schizophrenia
Karlsson, P., Farde, L., Halldin, C., & Sedvall, G. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.5.761 · Cited by 172 · see citing works
Self-citationPathogenesis of Tourette's Syndrome
Leckman, J. F., Peterson, B. S., Anderson, G. M., Arnsten, A. F. T., Pauls, D. L., & Cohen, D. J. (1997) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.1997.tb01508.x · Cited by 171 · see citing works
Lidow, M. S., & Rakic, P. (1992) · Cerebral Cortex · doi:10.1093/cercor/2.5.401 · Cited by 141 · see citing works
Effect of cocaine self-administration on dopamine D2 receptors in rhesus monkeys
Moore, R. J., Vinsant, S. L., Nader, M. A., Porrino, L. J., & Friedman, D. P. (1998) · Synapse · doi:10.1002/(sici)1098-2396(199809)30:1 · Cited by 134 · see citing works
Brain Neuroplasticity in Healthy, Hyperactive and Psychotic Children: Insights from Neuroimaging
Rapoport, J. L., & Gogtay, N. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301553 · Cited by 132 · see citing works
Araki, K. Y., Sims, J. R., & Bhide, P. G. (2007) · Brain Research · doi:10.1016/j.brainres.2007.04.043 · Cited by 131 · see citing works
Postnatal alterations in dopaminergic markers in the human prefrontal cortex
Weickert, C. S., Webster, M. J., Gondipalli, P., Rothmond, D., Fatula, R. J., Herman, M. M., Kleinman, J. E., & Akil, M. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2006.10.009 · Cited by 126 · see citing works
The Role of Dopamine Receptors in Regulating the Size of Axonal Arbors
Parish, C. L., Finkelstein, D. I., Drago, J., Borrelli, E., & Horne, M. K. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-14-05147.2001 · Cited by 121 · see citing works
Meng, S. Z., Ozawa, Y., Itoh, M., & Takashima, S. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01933-2 · Cited by 112 · see citing works
Activation of dopaminergic D1 receptors promotes morphogenesis of developing striatal neurons
Schmidt, U. G., Beyer, C., Oestreicher, A. B., Reisert, I., Schilling, K., & Pilgrim, C. (1996) · Neuroscience · doi:10.1016/0306-4522(96)00201-1 · Cited by 98 · see citing works
Jung, A. B., & Bennett, J. P. (1996) · Developmental Brain Research · doi:10.1016/0165-3806(96)00033-8 · Cited by 94 · see citing works
Guo, N., Hwang, D., Lo, E., Huang, Y.-Y., Laruelle, M. A., & Abi‐Dargham, A. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300224 · Cited by 93 · see citing works
The effect of aging on the D1 dopamine receptors in human frontal cortex
Keyser, J. D., Backer, J. D., Vauquelin, G., & Ebinger, G. (1990) · Brain Research · doi:10.1016/0006-8993(90)91672-4 · Cited by 93 · see citing works
Filloux, F. M., Wamsley, J. K., & Dawson, T. M. (1987) · Brain Research · doi:10.1016/0006-8993(87)90373-8 · Cited by 83 · see citing works
Lewis, D. A., Sesack, S. R., Levey, A. I., & Rosenberg, D. R. (1997) · Advances in pharmacology · doi:10.1016/s1054-3589(08)60845-5 · Cited by 71 · see citing works
Evolution of neuronal numerical density in the developing and aging human visual cortex.
Leuba, G., & Garey, L. J. (1987) · PubMed · Cited by 70 · see citing works
Stanwood, G. D., Parlaman, J. P., & Levitt, P. R. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20548 · Cited by 62 · see citing works
Reduced striatal D 1 receptor binding in autosomal dominant nocturnal frontal lobe epilepsy
Fedi, M., Berkovic, S. F., Scheffer, I. E., O'Keefe, G. J., Marini, C., Mulligan, R. S., Gong, S., Tochon‐Danguy, H., & Reutens, D. C. (2008) · Neurology · doi:10.1212/01.wnl.0000316192.52731.77 · Cited by 62 · see citing works
Developmental Regulation of the Dopamine D1 Receptor in Human Caudate and Putamen
Montague, D. C. (1999) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00062-7 · Cited by 61 · see citing works
A PET study of D1-like dopamine receptor ligand binding
Chou, Y.-H., Karlsson, P., Halldin, C., Olsson, H., & Farde, L. (1999) · Psychopharmacology · doi:10.1007/s002130051110 · Cited by 61 · see citing works
Self-citationButler, A. K., Uryu, K., & Chesselet, M. (1998) · Developmental Neuroscience · doi:10.1159/000017319 · Cited by 47 · see citing works
The Effect of Aging on Rat Striatal D1 Receptor mRNA-Containing Neurons
Zhang, L., & Roth, G. S. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00011-0 · Cited by 15 · see citing works
Huttenlocher (1997) · doi:10.1002/(sici)1096-9861(19971020)387:2
Flagged first, then by citations
Cited by
Sorted by citations
Influence of the COMT genotype on working memory and brain activity changes during development
Dumontheil, I., Roggeman, C., Ziermans, T., Peyrard-Janvid, M., Matsson, H., Kere, J., & Klingberg, T. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.02.027 · Cited by 165 · see citing works
Developmental changes in human dopamine neurotransmission: cortical receptors and terminators
Rothmond, D. A., Weickert, C. S., & Webster, M. J. (2012) · BMC Neuroscience · doi:10.1186/1471-2202-13-18 · Cited by 97 · see citing works
Prefrontal Dopaminergic Mechanisms of Extinction in Adolescence Compared to Adulthood in Rats
Zbukvic, I. C., Park, C. H. J., Ganella, D. E., Lawrence, A. J., & Kim, J. H. (2017) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2017.00032 · Cited by 57 · see citing works
Boecker-Schlier, R., Holz, N. E., Buchmann, A. F., Blomeyer, D., Plichta, M. M., Jennen-Steinmetz, C., Wolf, I., Baumeister, S., Treutlein, J., Rietschel, M., et al. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.02.006 · Cited by 42 · see citing works
Brancato, A., Castelli, V., Lavanco, G., Tringali, G., Micale, V., Kuchar, M., D’Amico, C., Pizzolanti, G., Feo, S., & Cannizzaro, C. (2021) · Biomedicines · doi:10.3390/biomedicines9091161 · Cited by 37 · see citing works
- Authors
- Jucaite, A., Forssberg, H., Karlsson, P., Halldin, C., & Farde, L.
- Affiliations
- Karolinska Institutet (SE)
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 167
- Issue
- 1
- Pages
- 104-110
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W1990866533
- Cited by
- 67
- References
- 61
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 2 · 2017: 4 · 2016: 6 · 2015: 2 · 2014: 7 · 2013: 7 · 2012: 5
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- dopamine D1 receptor, receptor density, age-related decline, brain development, adolescence, cerebral cortex, striatum, orbitofrontal cortex, posterior cingulate cortex, neurodevelopmental disorders
- MeSH terms
- Adolescent, Adult, Aging, Benzazepines, Brain, Brain Mapping, Carbon Radioisotopes, Child, Child Development, Cross-Sectional Studies, Female, Humans, Magnetic Resonance Imaging, Male, Receptors, Dopamine D1, Adolescent Development, Positron-Emission Tomography, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review