Developmental changes in dopamine neurotransmission in adolescence: behavioral implications and issues in assessment

Abstract

Adolescence is characterized by increased risk-taking, novelty-seeking, and locomotor activity, all of which suggest a heightened appetitive drive. The neurotransmitter dopamine is typically associated with behavioral activation and heightened forms of appetitive behavior in mammalian species, and this pattern of activation has been described in terms of a neurobehavioral system that underlies incentive-motivated behavior. Adolescence may be a time of elevated activity within this system. This review provides a summary of changes within cortical and subcortical dopaminergic systems that may account for changes in cognition and affect that characterize adolescent behavior. Because there is a dearth of information regarding neurochemical changes in human adolescents, models for assessing links between neurochemical activity and behavior in human adolescents will be described using molecular genetic techniques. Furthermore, we will suggest how these techniques can be combined with other methods such as pharmacology to measure the impact of dopamine activity on behavior and how this relation changes through the lifespan.

Figure 1

Dopamine Synthesis Pathway: Dopamine’s synthesis pathway begins with the amino acid tyrosine and is regulated by the activity of tyrosine hydroyxylase. As indicated in the figure, dopamine in neural synapses is regulated by monoamine oxydase (MAO) and catechol-O-methyltransferase (COMT) activity.

Figure 2

Dopamine’s Inverted-U-Shaped Performance Function and Lifespan Development: Dopamine regulates behavior according to an inverted U-shaped performance function. As discussed in the text, the nature of this function may change during the human lifespan. Higher levels of available dopamine in adolescence versus adulthood may push some individuals toward a more optimal position on the curve, while some individuals may be disadvantaged during this time due to levels that are too high.

Figure 3

Illustration of the COMT genotype-by-behavior association in an adolescent sample: Adolescents, ages 9 to 17, who varied in COMT genotype completed a battery of neurocognitive tasks that reflect dopamine activity. COMT Val/Met heterzygotes performed better than homozygotes on measures of working memory, attention, and motor function in accord with the model illustrated in Figure 2, suggesting that they experience relatively optimal levels of dopamine activity during this period of the lifespan. (From Wahlstrom et al., 2007, with permission).

Figure 4

COMT by Age Group Interaction: An expansion of the study described in Figure 3 allowed age-by-genotype interactions to be characterized. An age-by-genotype interaction was observed for attention and working memory function when comparing 9–12, 13–17 and 18–25 year-olds. As described in the text, individuals who carry the Val allele level off in their development of these skills prior to those who are Met homozygotes. Met-Met homozygotes show a developmental acceleration of performance from ages 13–17 to 18–25 that is not present in the other groups. Values represent estimated marginal means plus/minus one standard error.