Mesocorticolimbic Dopamine Pathways Across Adolescence: Diversity in Development

Abstract

Mesocorticolimbic dopamine circuity undergoes a protracted maturation during adolescent life. Stable adult levels of behavioral functioning in reward, motivational, and cognitive domains are established as these pathways are refined, however, their extended developmental window also leaves them vulnerable to perturbation by environmental factors. In this review, we highlight recent advances in understanding the mechanisms underlying dopamine pathway development in the adolescent brain, and how the environment influences these processes to establish or disrupt neurocircuit diversity. We further integrate these recent studies into the larger historical framework of anatomical and neurochemical changes occurring during adolescence in the mesocorticolimbic dopamine system. While dopamine neuron heterogeneity is increasingly appreciated at molecular, physiological, and anatomical levels, we suggest that a developmental facet may play a key role in establishing vulnerability or resilience to environmental stimuli and experience in distinct dopamine circuits, shifting the balance between healthy brain development and susceptibility to psychiatric disease.

Contributions of dopamine-related basal ganglia neurophysiology to the developmental effects of incentives on inhibitory control

“…Neurodevelopmental models, including the Driven Dual Systems model ( Luna and Wright, 2016 , Shulman et al, 2016 ), propose that developmental changes in dopamine (DA) and reward system function underlie this peak in sensation seeking ( Shulman et al, 2016 ), supported by a relative predominance of reward systems over cognitive control systems (including inhibitory control) that bias adolescent decision-making toward rewarding stimuli ( Luna and Wright, 2016 , Shulman et al, 2016 ). Though we are beginning to understand how DA function supports reward-driven behaviors during adolescence in both animal models ( Andersen et al, 1997 , Luciana et al, 2012 , Wahlstrom et al, 2010 ) and human studies ( Reynolds and Flores, 2021 ), far less is known about the role of DA in interactions between developmentally-relevant reward and inhibitory control systems.…”

Bi-phasic patterns of age-related differences in dopamine D1 receptors across the adult lifespan

“…The dopamine (DA) system undergoes profound changes across the lifespan, along with concomitant alterations in cognition ( (Bäckman et al, 2010;Islam et al, 2021;Li et al, 2010;Reynolds and Flores, 2021a;Wahlstrom et al, 2010), for reviews). In childhood and adolescence, ongoing maturation of the prefrontal DA system is associated with excessive DA activity (Islam et al, 2021;Reynolds and Flores, 2021a;Wahlstrom et al, 2010Wahlstrom et al, , 2007, constraining the development of executive functions (Diamond, 2009;Diamond et al, 2004;Diamond and Baddeley, 1996;Klune et al, 2021). At older ages, DA losses may result in insufficient DA modulation (Lindenberger et al, 2008;Nagel et al, 2008), and decline in multiple cognitive domains (Bäckman et al, 2000(Bäckman et al, , 2006Karalija et al, 2019;Nyberg et al, 2010;Volkow et al, 1998).…”

Association of Polymorphism within the Putative miRNA Target Site in the 3′UTR Region of the DRD2 Gene with Neuroticism in Patients with Substance Use Disorder

“…On the other hand, it has been proven that reward sensitivity, avoiding unpleasantness, and looking for pleasure are closely dependent on dopamine neurotransmission, and several active dopamine receptors [ 88 , 89 , 90 , 91 ]. In the prefrontal cortex, dopamine action is involved in the efficiency of cognitive functions [ 92 , 93 ], as well as in thoughts and emotional and behavioral processes using the meso–cortico–limbic pathway [ 94 ]. Finally, chronic substance abuse may lead to exaggerated dopamine turnover and a clinical response expressed in different psychiatric disturbances [ 95 ].…”