Developmental neurocircuitry of motivation in adolescence: a critical period of addiction vulnerability

Abstract

Objective: Epidemiological studies indicate that experimentation with addictive drugs and onset of addictive disorders is primarily concentrated in adolescence and young adulthood. The authors describe basic and clinical data supporting adolescent neurodevelopment as a biologically critical period of greater vulnerability for experimentation with substances and acquisition of substance use disorders.

Method: The authors reviewed recent literature regarding neurocircuitry underlying motivation, impulsivity, and addiction, with a focus on studies investigating adolescent neurodevelopment.

Results: Adolescent neurodevelopment occurs in brain regions associated with motivation, impulsivity, and addiction. Adolescent impulsivity and/or novelty seeking as a transitional trait behavior can be explained in part by maturational changes in frontal cortical and subcortical monoaminergic systems. These developmental processes may advantageously promote learning drives for adaptation to adult roles but may also confer greater vulnerability to the addictive actions of drugs.

Conclusions: An exploration of developmental changes in neurocircuitry involved in impulse control has significant implications for understanding adolescent behavior, addiction vulnerability, and the prevention of addiction in adolescence and adulthood.

FIGURE 1. Major Motivational Brain Circuitry Putatively Involved in Impulsivity, Decision Making, and Drug Addiction^a

^a Primary motivation circuitry directly subserves the neurocomputational events of decision making and the selection of motivational drives for behavioral action. These events are determined by subsystems integral to cortical-striatal-thalamic-cortical pathways (open yellow arrow) that can either promote or inhibit the enactment of motivated drives. Secondary motivation circuitry provides the input (affective, memory, sensory, hormonal/homeostatic information) that generates and influences the fate of motivational drives in primary motivation circuitry. Addictive drugs, primarily by virtue of neuroplastic changes associated with dopamine activity most highly concentrated in primary motivation circuitry, produce long-term motivational effects.

FIGURE 2. Cortical-Striatal-Thalamic-Cortical Loops Within Primary Motivation Circuitry Involved in the Representation of Motivated Drives and the Neurocomputational Events of Motivational Decision Making and Behavioral Instigation^a

^a Part A shows that glutamatergic afferents from the prefrontal cortex, in conjunction with those from the amygdala and hippocampus, convey executive, affective, and contextual memory information to the nucleus accumbens by influencing the firing patterns of neuronal ensembles in the nucleus accumbens, depicted as local peaks in firing rates. Nucleus accumbens architecture allows a vast number of motivational possibilities to be represented by a corresponding diversity of firing patterns. Motivational information is conveyed by GABA-ergic afferents to the ventral globus pallidus and then to the thalamus, which in turn influence cortical and subcortical centers of motor output. Part B shows that dopamine discharge in the nucleus accumbens (thickened red arrows) is implicated in the identification of environmental novelty, the actions of addictive drugs, and the gating of motivated drives into behavioral actions by changing responses of nucleus accumbens neurons to cortical and limbic glutamatergic afferents. These events are proposed to lead to relative extremes in firing patterns among nucleus accumbens neuronal ensembles, depicted as increases in local peak amplitudes that code for behaviorally activating events in downstream motor systems. These events may also facilitate mechanisms of neuroplasticity among nucleus accumbens neurons and their afferents, determining the future repertoire of motivational drive representations and/or thresholds for behavioral instigation. During adolescence, ongoing frontal cortical maturation (limiting motivational inhibitory capacity), along with robust novelty-encoding dopamine activity, may enhance the action of addictive drugs to cause the system to operate in a promotional motivated state (as in B), producing more profound long-term motivational consequences.