Developmental changes in human dopamine neurotransmission: cortical receptors and terminators
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BACKGROUND: Dopamine is integral to cognition, learning and memory, and dysfunctions of the frontal cortical dopamine system have been implicated in several developmental neuropsychiatric disorders. The dorsolateral prefrontal cortex (DLPFC) is critical for working memory which does not fully mature until the third decade of life. Few studies have reported on the normal development of the dopamine system in human DLPFC during postnatal life. We assessed pre- and postsynaptic components of the dopamine system including tyrosine hydroxylase, the dopamine receptors (D1, D2 short and D2 long isoforms, D4, D5), catechol-O-methyltransferase, and monoamine oxidase (A and B) in the developing human DLPFC (6 weeks -50 years). RESULTS: Gene expression was first analysed by microarray and then by quantitative real-time PCR. Protein expression was analysed by western blot. Protein levels for tyrosine hydroxylase peaked during the first year of life (p < 0.001) then gradually declined to adulthood. Similarly, mRNA levels of dopamine receptors D2S (p < 0.001) and D2L (p = 0.003) isoforms, monoamine oxidase A (p < 0.001) and catechol-O-methyltransferase (p = 0.024) were significantly higher in neonates and infants as was catechol-O-methyltransferase protein (32 kDa, p = 0.027). In contrast, dopamine D1 receptor mRNA correlated positively with age (p = 0.002) and dopamine D1 receptor protein expression increased throughout development (p < 0.001) with adults having the highest D1 protein levels (p ≤ 0.01). Monoamine oxidase B mRNA and protein (p < 0.001) levels also increased significantly throughout development. Interestingly, dopamine D5 receptor mRNA levels negatively correlated with age (r = -0.31, p = 0.018) in an expression profile opposite to that of the dopamine D1 receptor. CONCLUSIONS: We find distinct developmental changes in key components of the dopamine system in DLPFC over postnatal life. Those genes that are highly expressed during the first year of postnatal life may influence and orchestrate the early development of cortical neural circuitry while genes portraying a pattern of increasing expression with age may indicate a role in DLPFC maturation and attainment of adult levels of cognitive function.
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A similar surge in regional-specific dopaminergic connectivity to the PFC can be observed in primates, including human, modulating local microcircuits.
“A similar surge in regional-specific dopaminergic connectivity to the PFC can be observed in primates, including human modulating local microcircuits [165–169].”
From Development of prefrontal cortex (2022) · cites this paper as [168]
The Discussion (page not given) reports developmental changes in dopamine-related proteins in the human DLPFC and suggests that dopamine innervation may become more targeted as circuitry is refined. It does not report an observed surge in region-specific dopaminergic connectivity or demonstrate modulation of local microcircuits; the Results instead report that tyrosine hydroxylase levels decline after infancy. (LLM, conf=0.84)
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- Authors
- Rothmond, D. A., Weickert, C. S., & Webster, M. J.
- Affiliations
- Schizophrenia Research Institute (AU)
- UNSW Sydney (AU)
- Corresponding author
- Rothmond, Debora A
- Venue
- BMC Neuroscience
- Published
- 2012-02-15
- Volume
- 13
- Issue
- 1
- Pages
- 18-18
- ISSN
- 1471-2202 (ISSN-L)
- PMC
- PMC3315415
- OpenAlex
- W2039672508
- Cited by
- 97
- References
- 81
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 10 · 2023: 7 · 2022: 14 · 2021: 9 · 2020: 6 · 2019: 5 · 2018: 7 · 2017: 9 · 2016: 5 · 2015: 7 · 2014: 3 · 2013: 7 · 2012: 3
- FWCI
- 2.64
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Neuroscience Research Australia
- University of New South Wales
- Macquarie Group Foundation
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- dopamine signaling, dorsolateral prefrontal cortex, brain development, dopamine receptors, dopamine D1 receptor, dopamine D5 receptor, tyrosine hydroxylase, catechol-O-methyltransferase, monoamine oxidase, postsynaptic receptors, presynaptic terminals, working memory, postnatal development, gene expression, protein expression
- MeSH terms
- Adolescent, Adult, Age Factors, Analysis of Variance, Catechol O-Methyltransferase, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Middle Aged, Monoamine Oxidase, Receptors, Dopamine, RNA, Messenger, Tyrosine 3-Monooxygenase, Cohort Studies, Prefrontal Cortex, Gene Expression Regulation, Developmental, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Young Adult
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