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Open Access Highly Accessed Research article

Developmental changes in human dopamine neurotransmission: cortical receptors and terminators

Debora A Rothmond123*, Cynthia S Weickert123 and Maree J Webster4

Author affiliations

1 Schizophrenia Research Institute, 405 Liverpool St, Darlinghurst NSW 2010 AU

2 Neuroscience Research Australia, Schizophrenia Research Laboratory, Barker St, Randwick NSW 2031 AU

3 University of New South Wales, Faculty of Medicine, School of Psychiatry, Hospital Rd, Randwick, NSW 2031 AU

4 Stanley Laboratory of Brain Research, 9800 Medical Center Dr, Bldg. 2C-Rm C050, Rockville, MD, USA 20850

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Citation and License

BMC Neuroscience 2012, 13:18  doi:10.1186/1471-2202-13-18

Published: 15 February 2012

Abstract

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.

Keywords:
DLPFC; postmortem; ADHD; schizophrenia; dopamine receptor; tyrosine hydroxylase; COMT; MAOA; MAOB; DRD