Developmental changes in human dopamine neurotransmission: cortical receptors and terminators

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.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.The prefrontal cortex (PFC), particularly the dorsolateral prefrontal cortex (DLPFC), is markedly expanded and differentiated in the primate brain. In humans, the DLPFC [1,2] and hence adult level performance in working memory [3-5] may not fully mature until young adulthood. The functional integrity of the PFC is sensitive to modulation by catecholamines, particularly dopamine (DA) [6-8]. Indeed, DA is essential to the development and function of PFC controlled tasks of working memory, attention, behavio