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.

Introduction

As reviewed by other papers within this issue and in the literature as a whole, adolescence is characterized by widespread neurobiological changes such as shifts in brain matter composition (see papers by Paus, Gogtay, Thompson, and Schmithorst (this issue)), modifications of neural synchrony (Uhlhaas et al., 2009), increased hormonal release (Styne, 1994), and neurochemical alterations (Doremus-Fitzwater et al., this issue; Spear, 2000). Much of this work has focused on changes in brain structure as well as attempts to define adolescent-unique patterns of functional brain activity in the context of cognitive and emotional behaviors (see papers by Luna et al. (this issue) and Somerville et al. (this issue)). This latter set of findings has identified brain regions where activation patterns are distinct in adolescents versus children and adults as they perform cognitive and emotional tasks, leading to renewed conceptualizations of brain systems that operate in a distinctive manner during this period of the lifespan (Bjork et al., 2004, Bunge et al., 2002, Ernst et al., 2005, Galvan et al., 2006, Luna et al., 2004, May et al., 2004). Moreover, it is clear that adolescents differ from adults on behavioral measures of decision-making, planning, working memory, and inhibitory control (Asato et al., 2006, Crone and van der Molen, 2004, Hooper et al., 2004, Luciana et al., 2009, Luciana et al., 2005, Luna et al., 2004). That said, it has been a challenge to definitively associate the changes in neuroarchitecture that have been described across adolescence with changing patterns of behavior during this period of the lifespan, particularly with respect to risk-taking and aspects of behavioral regulation. Age-related sources of variation in structure–function relations are relatively small in magnitude (Olson et al., 2009, Schmithorst et al., 2005, Shaw et al., 2006), and some structure–function relations are not easily attributable to maturational processes (Olesen, Nagy, Westerberg, & Klingberg, 2003). Given that adolescence is a period in the lifespan characterized by alarming increases in risk-taking behaviors and that these behavioral patterns are relatively impervious to educational interventions (Steinberg, 2008), it has become commonplace to assert that they have a basis in brain development. Synaptic structure is becoming refined during adolescence, and the prefrontal cortex (PFC) may be among the last regions to attain a maturational plateau. Recent formulations have emphasized that adolescent patterns of frontal–limbic integration are different from what has been observed in adults and children (Fareri et al., 2008, Galvan et al., 2006). However, none of these brain substrates definitively underlies adolescents’ tendencies to select risky alternatives when faced with options that are probabilistically risky versus safe or their tendencies to seek out situations where there is an increased opportunity for risk-taking. Thus, perhaps there are other brain–behavior associations, in combination with existing approaches, which should receive greater scrutiny within empirical studies. For instance, it is unknown whether age-related changes in neurochemistry would better account for the changing behavioral patterns that are observed during adolescence. The direct study of neurochemistry in human developmental samples has remained elusive, primarily because of difficulties in measuring chemical substrates using non-invasive procedures. The overarching purpose of this review is to outline a rationale for the direct examination, in humans, of neurochemical substrates that may underlie individual differences in adolescent risk-seeking and subsequent risk-taking. One exemplar within the monoaminergic transmitter system will be highlighted.

At the outset, it should be emphasized that, in our view, a particularly salient feature of behavior that is viewed as problematic in adolescents concerns the failure to choose the less risky versus more risky alternative when faced with a situation where there are signals regarding the positive and negative outcomes associated with each potential choice. Perhaps more than one alternative cannot be simultaneously appreciated, and there is an information processing failure. Or perhaps the weighting of outcomes between alternatives is skewed such that there is an imbalance across motivational systems that might otherwise moderate behavior. It may be that positive outcomes are extremely salient, that negative outcomes are less salient than at other points in the lifespan, or that negative outcomes are not appreciated at all. Alternatively, perhaps all potential outcomes are equally salient and weighed but for some reason, risky alternatives are selected such that there is a response bias. In deciphering these possibilities, it is important to consider, then, how multiple potential behavioral choices gain access to information processing networks, how each choice is evaluated in terms of positive and negative outcome contingencies, and how response selection takes place.

In addressing these issues, the monoamines have been of specific interest because of extensive data linking their activity to multiple domains of affect, cognition, and motor behaviors (Depue and Spoont, 1986, Mattay et al., 2002, Sawaguchi and Goldman-Rakic, 1994, Wise, 2004), as well as psychiatric disorders such as depression, schizophrenia, and substance abuse (Eison and Eison, 1994, Weinberger, 1987, Wise, 1998). These associations may be especially relevant to adolescence, given the broad changes in cognition and affect that occur during this time as well as increased rates of psychiatric disorders (Costello et al., 1999, Kessler et al., 2005, Paus et al., 2008, Shedler and Block, 1990, Szymanski et al., 1995). One perspective is that discrete monoaminergic transmitter systems promote integrated and systematized behaviors that are adaptive to the species as a whole but are problematic for some individuals.