Dopamine, Ego-Depletion, and Withdrawal: How Sequential Task Paradigms Model Phenotypes of Substance Use Disorders

Frequent relapse in substance use disorders signals a need to consider novel interventions to improve treatment outcomes (e.g., neuromodulation). Yet, much of the research supporting these interventions is preliminary which may delay their implementation in clinical practice. To expand this evidence base, we suggest addiction researchers consider the sequential task paradigm for modelling symptoms of withdrawal within the general population to accelerate generation of evidence to support and guide development of interventions. Despite the recent debate concerning legitimacy of ego-depletion, sequential task paradigms ubiquitous in this literature increase appetitive motivations which drive impulsivity, in addition to weakening avoidance motivations which guide top-down processing and inhibition. These motivational shifts mirror phenotypes of withdrawal, with physiological and imaging evidence indicating shared neural mechanisms (e.g., orbitofrontal cortex). Importantly, we suggest discrepancies in dopaminergic activity are responsible for these overlapping features of ego-depletion and withdrawal. Sequential task paradigms are posited to reduce mesolimbic dopamine activity via deprivation of natural reinforcers, whereas downregulation of dopamine receptors and production promote reliance on highly rewarding behaviors (e.g., drugs) to reach expected stimulation during withdrawal. Despite differing mechanisms, both phenomena are driven by disparities in expected versus observed dopamine activity of reward pathways. Notably, these discrepancies in mesolimbic activity enhance attention toward appetitive stimuli which may restore hypoactive dopamine pathways, while simultaneously undermining attempts to stop impulses guided by these approach motivations. Thus, sequential task paradigms may reduce barriers for those interested in conducting research on addiction, widening participation to improve treatment outcomes and reduce relapse.