Vigor, Effort-Related Aspects of Motivation and Anhedonia.

In this chapter we provide an overview of the pharmacological and circuit mechanisms that determine the willingness to expend effort in pursuit of rewards. A particular focus will be on the role of the mesolimbic dopamine system, as well the contributing roles of limbic and cortical brains areas involved in the evaluation, selection, and invigoration of goal-directed actions. We begin with a review of preclinical studies, which have provided key insights into the brain systems that are necessary and sufficient for effort-based decision-making and have characterized novel compounds that enhance selection of high-effort activities. Next, we summarize translational studies identifying and expanding this circuitry in humans. Finally, we discuss the relevance of this work for understanding common motivational impairments as part of the broader anhedonia symptom domain associated with mental illness, and the identification of new treatment targets within this circuitry to improve motivation and effort-expenditure.